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Alzheimerʼs Disease

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Springer Handbook of Bio-/Neuroinformatics

Part of the book series: Springer Handbooks ((SHB))

Abstract

Alzheimerʼ s disease (AD) is the most common neurodegenerative disorder in late life which is clinically characterized by dementia and progressive cognitive impairments with presently no effective treatment. This chapter summarizes recent progress achieved during the last decades in understanding the pathogenesis of AD. Basing on the pathomorphological hallmarks (senile amyloid plaque deposits, occurance of neurofibrillary tangles as hyperphosphorylated tau protein in cerebral cortex and hippocampus) and other consistent features of the disease (neurodegeneration, cholinergic dysfunction, vascular impairments), the mayor hypotheses of cause and development of the sporadic, not genetically inherited, AD are described. Finally, to reflect the disease in its entirety and internal connective relationships, the different pathogenetic hypotheses are tentatively combined to describe the interplay of the essential features of AD and their mutually influencing pathogenetic processes in a unified model. Such a unified approach may provide a basis to model pathogenesis and progression of AD by application of computational methods such as the recently introduced novel research framework for building probabilistic computational neurogenetic models (pCNGM) by Kasabov and coworkers [51.1].

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Abbreviations

β-CTF:

β-carboxy-terminal fragment

Aβ:

β-amyloid peptide

ACh:

muscarinic acetylcholine

AChE:

acetylcholinesterase

AD:

Alzheimerʼs disease

ADAM:

a disintegrin and metalloproteinase

ADDL:

amyloid-derived diffusible ligand

AICD:

intracellular domain of APP

APH-1:

anterior pharynx-defective-1

APP:

amyloid precursor protein

BACE:

β-site APP cleaving enzyme

BDNF:

brain-derived neurotrophic factor

CAA:

cerebral amyloid angiopathy

CBF:

cerebral blood flow

CDK5:

cyclin-dependent kinase 5

CTF:

carboxy-terminal fragment

ChAT:

choline acetyltransferase

CoA:

coenzyme A

DR6:

death receptor 6

DYRK1A:

dual specificity tyrosine-phosphorylation-regulated kinase1A

EEG:

electroencephalography

EGFR:

epidermal growth factor receptor

ER:

endoplasmic reticulum

ERK2:

extracellular signal-related kinase 2

ERK:

extracellular signal-regulated kinase

FAD:

familial AD

GABA:

gamma-aminobutyric acid

GDP:

guanosine diphosphate

GRK:

G protein-coupled receptor kinase

GSK:

glycogen synthase kinase

GTP:

guanosine triphosphate

IL-1β :

interleukin-1β

IT:

infero temporal cortex

JAK/STAT:

Januskinase/signal transducers and activators of transcription

KPI:

Kunitz protease inhibitor

LM MDR:

log-linear model-based multifactor dimensionality reduction

LRP1:

lipoprotein receptor-related protein 1

LTP:

long-term potentiation

MAP:

maximum a posteriori

MAPK:

mitogen-activated protein kinase

MCI:

mild cognitive impairment

MEG:

magnetoencephalography

NADPH:

nicotinamide adenine dinucleotide phosphate

NAPP:

N-terminal fragment of amyloid precursor protein

NGF:

nerve growth factor

NO:

nitric oxide

PC12:

pheochromocytoma 12

PDAPP:

PD amyloid precursor protein

PEN-2:

presenilin-enhancer-2

PFK:

phosphofructokinase

PHF:

paired helical filament

PI3K:

phosphatidylinositol 3-kinase

PKA:

protein kinase A

PKC:

protein kinase C

PPI:

protein–protein interaction

PRN:

protein regulatory network

QSAR:

quantitative structure-activity relationship

RAGE:

receptor for advanced glycation end products

SF:

straight filament

SNP:

single-nucleotide polymorphism

SORL:

sortilin-related sorting receptor

TGF:

transforming growth factor

TNF:

tumor necrosis factor

Tg:

transgenic

VAChT:

vesicular acetylcholine transporter

VEGF:

vascular endothelial growth factor

VIP:

vasoactive intestinal peptide

fMRI:

functional magnetic resonance imaging

log:

logistic regression

mAChR:

cholinergic muscarinic receptor

mRNA:

messenger RNA

nAChR:

nicotinic acetylcholine receptor

p38-MAP:

P38 mitogen-activated protein

p75NTR:

p75 neurotrophin receptor

pCNGM:

probabilistic computational neurogenetic model

pSNN:

probabilistic spiking neural network

proNGF:

NGF precursor

siRNA:

small interfering RNA

trkA:

high-affinity receptor

References

  1. N.K. Kasabov, R. Schliebs, H. Kojima: Probabilistic computational neurogenetic modeling: From cognitive systems to Alzheimerʼs disease, IEEE Trans. Auton. Mental Dev. 3, 1–12 (2011)

    Article  Google Scholar 

  2. A. Alzheimer: Über eine eigenartige Erkrankung der Hirnrinde, Allg. Z. Psychiatr. Psychisch-Gerichtl. Med. 64, 146–148 (1907)

    Google Scholar 

  3. G.G. Glenner, C.W. Wong: Alzheimerʼs disease and Downʼs syndrome: Sharing of a unique cerebrovascular amyloid fibril protein, Biochem. Biophys. Res. Commun. 122, 1131–1135 (1984)

    Article  Google Scholar 

  4. C.L. Masters, G. Simms, N.A. Weinman, G. Multhaup, B.L. McDonald, K. Beyreuther: Amyloid plaque core protein in Alzheimer disease and down syndrome, Proc. Natl. Acad. Sci. USA 82, 4245–4249 (1985)

    Article  Google Scholar 

  5. J. Kang, H.G. Lemaire, A. Unterbeck, J.M. Salbaum, C.L. Masters, K.H. Grzeschik, G. Multhaup, K. Beyreuther, B. Müller-Hill: The precursor of Alzheimerʼs disease amyloid A4 protein resembles a cell-surface receptor, Nature 325, 733–736 (1987)

    Article  Google Scholar 

  6. D. Goldgaber, M.I. Lerman, O.W. McBride, U. Saffiotti, D.C. Gajdusek: (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimerʼs disease, Science 235, 877–880 (2006)

    Article  Google Scholar 

  7. N.K. Robakis, N. Ramakrishna, G. Wolfe, H.M. Wisniewski: Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides, Proc. Natl. Acad. Sci. USA 84, 4190–4194 (1987)

    Article  Google Scholar 

  8. R.E. Tanzi, J.F. Gusella, P.C. Watkins, G.A. Bruns, P. St George-Hyslop, M.L. Van Keuren, D. Patterson, S. Pagan, D.M. Kurnit, R.L. Neve: Amyloid β protein gene: CDNA, mRNA distribution, and genetic linkage near the Alzheimer locus, Science 235, 880–884 (1987)

    Article  Google Scholar 

  9. H. Bickel: Die Epidemiologie der Demenz, Informationsblatt (Deutsche Alzheimer Gesellschaft e.V., Berlin 2010), available online at www.deutsche-alzheimer.de/

    Google Scholar 

  10. K. Herrup: Reimagining Alzheimerʼs disease–an age-based hypothesis, J. Neurosci. 30, 16755–16762 (2010)

    Article  Google Scholar 

  11. R.S. Turner: Alzheimerʼs disease, Semin. Neurol. 26, 499–506 (2006)

    Article  Google Scholar 

  12. R.J. Castellani, R.K. Rolston, M.A. Smith: Alzheimer disease, Dis. Mon. 56, 484–546 (2010)

    Article  Google Scholar 

  13. G.G. Glenner, C.W. Wong, V. Quaranta, E.D. Eanes: The amyloid deposits in Alzheimerʼs disease: Their nature and pathogenesis, Appl. Pathol. 2, 357–369 (1984)

    Google Scholar 

  14. I. Grundke-Iqbal, K. Iqbal, Y.C. Tung, M. Quinlan, H.M. Wisniewski, L.I. Binder: Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology, Proc. Natl. Acad. Sci. USA 83, 4913–4917 (1986)

    Article  Google Scholar 

  15. I. Grundke-Iqbal, K. Iqbal, M. Quinlan, Y.C. Tung, M.S. Zaidi, H.M. Wisniewski: Microtubule-associated protein tau. A component of Alzheimer paired helical filaments, J. Biol. Chem. 261, 6084–6089 (1986)

    Google Scholar 

  16. K. Iqbal, I. Grundke-Iqbal, A.J. Smith, L. George, Y.C. Tung, T. Zaidi: Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease, Proc. Natl. Acad. Sci. USA 86, 5646–5650 (1989)

    Article  Google Scholar 

  17. R. Lee, P. Kermani, K.K. Teng, B.L. Hempstead: Regulation of cell survival by secreted proneurotrophins, Science 294, 1945–1948 (2001)

    Article  Google Scholar 

  18. K. Iqbal, C. Alonso Adel, S. Chen, M.O. Chohan, E. El-Akkad, C.X. Gong, S. Khatoon, B. Li, F. Liu, A. Rahman, H. Tanimukai, I. Grundke-Iqbal: Tau pathology in Alzheimer disease and other tauopathies, Biochim. Biophys. Acta 1739, 198–210 (2005)

    Article  Google Scholar 

  19. A. Alonso, T. Zaidi, M. Novak, I. Grundke-Iqbal, K. Iqbal: Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments, Proc. Natl. Acad. Sci. USA 98, 6923–6928 (2001)

    Article  Google Scholar 

  20. K.R. Patterson, C. Remmers, Y. Fu, S. Brooker, N.M. Kanaan, L. Vana, S. Ward, J.F. Reyes, K. Philibert, M.J. Glucksman, L.I. Binder: Characterization of prefibrillar tau oligomers in vitro and in Alzheimer disease, J. Biol. Chem. 286, 23063–23076 (2011)

    Article  Google Scholar 

  21. C. Ballard, S. Gauthier, A. Corbett, C. Brayne, D. Aarsland, E. Jones: Alzheimerʼs disease, Lancet 377, 1019–1031 (2011)

    Article  Google Scholar 

  22. M.S. Wolfe: Tau mutations in neurodegenerative diseases, J. Biol. Chem. 284, 6021–6025 (2009)

    Article  Google Scholar 

  23. M. Goedert, M.G. Spillantini: A century of Alzheimerʼs disease, Science 314, 777–781 (2006)

    Article  Google Scholar 

  24. S.A. Small, K. Duff: Linking Aβ and tau in late-onset Alzheimerʼs disease: A dual pathway hypothesis, Neuron 60, 534–542 (2008)

    Article  Google Scholar 

  25. L. Bertram, C.M. Lill, R.E. Tanzi: The genetics of Alzheimer disease: Back to the future, Neuron 68, 270–281 (2010)

    Article  Google Scholar 

  26. E.H. Corder, A.M. Saunders, W.J. Strittmatter, D.E. Schmechel, P.C. Gaskell, G.W. Small, A.D. Roses, J.L. Haines, M.A. Pericak-Vance: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimerʼs disease in late onset families, Science 261, 921–923 (1993)

    Article  Google Scholar 

  27. A.M. Saunders, W.J. Strittmatter, D. Schmechel, P.H. George-Hyslop, M.A. Pericak-Vance, S.H. Joo, B.L. Rosi, J.F. Gusella, D.R. Crapper-MacLachlan, M.J. Alberts, C. Hulette, B. Crain, D. Goldgaber, A.D. Roses: Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimerʼs disease, Neurology 43, 467–1472 (1993)

    Article  Google Scholar 

  28. Y. Huang: Aβ-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimerʼs disease, Trends Mol. Med. 16, 287–294 (2010)

    Article  Google Scholar 

  29. E. Rogaeva, Y. Meng, J.H. Lee, Y. Gu, T. Kawarai, F. Zou, T. Katayama, C.T. Baldwin, R. Cheng, H. Hasegawa, F. Chen, N. Shibata, K.L. Lunetta, R. Pardossi-Piquard, C. Bohm, Y. Wakutani, L.A. Cupples, K.T. Cuenco, R.C. Green, L. Pinessi, I. Rainero, S. Sorbi, A. Bruni, R. Duara, R.P. Friedland, R. Inzelberg, W. Hampe, H. Bujo, Y.Q. Song, O.M. Andersen, T.E. Willnow, N. Graff-Radford, R.C. Petersen, D. Dickson, S.D. Der, P.E. Fraser, G. Schmitt-Ulms, S. Younkin, R. Mayeux, L.A. Farrer, P. St George-Hyslop: The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease, Nat. Genet. 39, 168–177 (2007)

    Article  Google Scholar 

  30. K. Morgan: The three new pathways leading to AD, Neuropathol. Appl. Neurobiol. 37, 353–357 (2011)

    Article  Google Scholar 

  31. D.M. Bowen, C.B. Smith, P. White, A.N. Davison: Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies, Brain 99, 459–496 (1976)

    Article  Google Scholar 

  32. P. Davies, A.J. Maloney: Selective loss of central cholinergic neurons in Alzheimerʼs disease, Lancet 2, 1403 (1976)

    Article  Google Scholar 

  33. E.K. Perry, P.H. Gibson, G. Blessed, R.H. Perry, B.E. Tomlinson: Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue, J. Neurol. Sci. 34, 247–265 (1977)

    Article  Google Scholar 

  34. E.K. Perry, R.H. Perry, G. Blessed, B.E. Tomlinson: Necropsy evidence of central cholinergic deficits in senile dementia, Lancet. 1, 189 (1977)

    Article  Google Scholar 

  35. D.S. Auld, T.J. Kornecook, S. Bastianetto, R. Quirion: Alzheimerʼs disease and the basal forebrain cholinergic system: Relations to β-amyloid peptides, cognition, and treatment strategies, Prog. Neurobiol. 68, 209–245 (2002)

    Article  Google Scholar 

  36. A. Nordberg: Neuroreceptor changes in Alzheimer disease, Cerebrovasc. Brain Metab. Rev. 4, 303–328 (1992)

    Google Scholar 

  37. L.M. Bierer, V. Haroutunian, S. Gabriel, P.J. Knott, L.S. Carlin, D.P. Purohit, D.P. Perl, J. Schmeidler, P. Kanof, K.L. Davis: Neurochemical correlates of dementia severity in Alzheimerʼs disease: Relative importance of the cholinergic deficits, J. Neurochem. 64, 749–760 (1995)

    Article  Google Scholar 

  38. W. Gsell, G. Jungkunz, P. Riederer: Functional neurochemistry of Alzheimerʼs disease, Curr. Pharmacol. Des. 10, 265–293 (2004)

    Article  Google Scholar 

  39. R.T. Bartus: On neurodegenerative diseases, models, and treatment strategies: Lessons learned and lessons forgotten a generation following the cholinergic hypothesis, Exp. Neurol. 163, 495–529 (2000)

    Article  Google Scholar 

  40. E.J. Mufson, S.E. Counts, S.E. Perez, S.D. Ginsberg: Cholinergic system during the progression of Alzheimerʼs disease: Therapeutic implications, Exp, Rev. Neurother. 8, 1703–1718 (2008)

    Article  Google Scholar 

  41. E.J. Mufson, S.E. Counts, M. Fahnestock, S.D. Ginsberg: Cholinotrophic molecular substrates of mild cognitive impairment in the elderly, Curr. Alzheimer Res. 4, 340–350 (2007)

    Article  Google Scholar 

  42. A.C. Cuello, M.A. Bruno, K.F. Bell: NGF-cholinergic dependency in brain aging, MCI and Alzheimerʼs disease, Curr. Alzheimer Res. 4, 351–358 (2007)

    Article  Google Scholar 

  43. Y.W. Zhang, R. Thompson, H. Zhang, H. Xu: APP processing in Alzheimerʼs disease, Mol. Brain 4, 3 (2011), doi: 10.1186/1756-6606-4-3

    Article  Google Scholar 

  44. A. Nikolaev, T. McLaughlin, D.D. OʼLeary, M. Tessier-Lavigne: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases, Nature 457, 981–989 (2009)

    Article  Google Scholar 

  45. H. Li, B. Wang, Z. Wang, Q. Guo, K. Tabuchi, R.E. Hammer, T.C. Südhof, H. Zheng: Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP, Proc. Natl. Acad. Sci. USA 107, 17362–17367 (2010)

    Article  Google Scholar 

  46. B. De Strooper, R. Vassar, T. Golde: The secretases: Enzymes with therapeutic potential in Alzheimer disease, Nat. Rev. Neurol. 6, 99–107 (2010)

    Article  Google Scholar 

  47. J. Hardy, D. Allsop: Amyloid deposition as the central event in the aetiology of Alzheimerʼs disease, Trends Pharmacol. Sci. 12, 383–388 (1991)

    Article  Google Scholar 

  48. J. Hardy: The amyloid hypothesis for Alzheimerʼs disease: A critical reappraisal, J. Neurochem. 110, 1129–1134 (2009)

    Article  Google Scholar 

  49. B.K. Harvey, C.T. Richie, B.J. Hoffer, M. Airavaara: Transgenic animal models of neurodegeneration based on human genetic studies, J. Neural Transm. 118, 27–45 (2011)

    Article  Google Scholar 

  50. A. Thathiah, B. De Strooper: The role of G protein-coupled receptors in the pathology of Alzheimerʼs disease, Nat. Rev. Neurosci. 12, 73–87 (2011)

    Article  Google Scholar 

  51. M. Pákáski, J. Kálmán: Interactions between the amyloid and cholinergic mechanisms in Alzheimerʼs disease, Neurochem. Int. 53, 103–111 (2008)

    Article  Google Scholar 

  52. R.H. Parri, T.K. Dineley: Nicotinic acetylcholine receptor interaction with beta-amyloid: Molecular, cellular, and physiological consequences, Curr. Alzheimer Res. 7, 27–39 (2010)

    Article  Google Scholar 

  53. M.M. Mesulam: Alzheimer plaques and cortical cholinergic innervation, Neuroscience 17, 275–276 (1986)

    Article  Google Scholar 

  54. M.A. Moran, E.J. Mufson, P. Gomez-Ramos: Colocalization of cholinesterases with β-amyloid protein in aged and Alzheimerʼs brain, Acta Neuropathol. 85, 362–369 (1993)

    Article  Google Scholar 

  55. R.M. Nitsch, B.E. Slack, R.J. Wurtman, J.H. Growdon: Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors, Science 258, 304–307 (1992)

    Article  Google Scholar 

  56. J.D. Buxbaum, M. Oishi, H.I. Chen, R. Pinkas-Kramarski, E.A. Jaffe, S.E. Gandy, P. Greengard: Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer β/A4 amyloid protein precursor, Proc. Natl. Acad. Sci. USA 89, 10075–10078 (1992)

    Article  Google Scholar 

  57. R.M. Nitsch, S.A. Farber, J.H. Growdon, R.J. Wurtman: Release of amyloid beta-protein precursor derivatives by electrical depolarization of rat hippocampal slices, Proc. Natl. Acad. Sci. USA 90, 5191–5193 (1993)

    Article  Google Scholar 

  58. H.A. Ensinger, H.N. Doods, A.R. Immel-Sehr, F.J. Kuhn, G. Lambrecht, K.D. Mendla, R.E. Muller, E. Mutschler, A. Sagrada, G. Walther: WAL 2014–a muscarinic agonist with preferential neuron-stimulating properties, Life Sci. 52, 473–480 (1993)

    Article  Google Scholar 

  59. S.A. Farber, R.M. Nitsch, J.G. Schulz, R.J. Wurtman: Regulated secretion of beta-amyloid precursor protein in rat brain, J. Neurosci. 15, 7442–7451 (1995)

    Google Scholar 

  60. A. Walland, S. Burkard, R. Hammer, W. Troger: In vivo consequences of M1-receptor activation by talsaclidine, Life Sci. 60, 977–984 (1997)

    Article  Google Scholar 

  61. D.M. Müller, K. Mendla, S.A. Farber, R.M. Nitsch: Muscarinic M1 receptor agonists increase the secretion of the amyloid precursor protein ectodomain, Life Sci. 60, 985–991 (1997)

    Article  Google Scholar 

  62. C. Hock, A. Maddalena, A. Raschig, F. Müller-Spahn, G. Eschweiler, K. Hager, I. Heuser, H. Hampel, T. Müller-Thomsen, W. Oertel, M. Wienrich, A. Signorell, C. Gonzalez-Agosti, R.M. Nitsch: Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta 42 in patients with Alzheimerʼs disease, Amyloid 10, 1–6 (2003)

    Article  Google Scholar 

  63. R.M. Nitsch: Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of Aβ42 in patients with Alzheimerʼs disease, Amyloid 10, 1–6 (2003)

    Article  Google Scholar 

  64. A.Y. Hung, C. Haass, R.M. Nitsch, W.Q. Qiu, M. Citron, R.J. Wurtman, J.H. Growdon, D.J. Selkoe: Activation of protein kinase C inhibits cellular production of the amyloid beta-protein, J. Biol. Chem. 268, 22959–22962 (1993)

    Google Scholar 

  65. M. Cisse, U. Braun, M. Leitges, A. Fisher, G. Pages, F. Checler, B. Vincent: ERK1-independent α-secretase cut of β-amyloid precursor protein via M1 muscarinic receptors and PKCα/ε, Mol. Cell Neurosci. 47, 223–232 (2011)

    Article  Google Scholar 

  66. B.E. Slack, J. Breu, M.A. Petryniak, K. Srivastava, R.J. Wurtman: Tyrosine phosphorylation-dependent stimulation of amyloid precursor protein secretion by the m3 muscarinic acetylcholine receptor, J. Biol. Chem. 270, 8337–8344 (1995)

    Article  Google Scholar 

  67. R. Haring, A. Fisher, D. Marciano, Z. Pittel, Y. Kloog, A. Zuckerman, N. Eshhar, E. Heldman: Mitogen-activated protein kinase-dependent and protein kinase C-dependent pathways link the m1 muscarinic receptor to beta-amyloid precursor protein secretion, J. Neurochem. 71, 2094–2103 (1998)

    Article  Google Scholar 

  68. S. Roßner, U. Ueberham, R. Schliebs, J.R. Perez-Polo, V. Bigl: The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signaling, Prog. Neurobiol. 56, 541–569 (1998)

    Article  Google Scholar 

  69. L. Lin, B. Georgievska, A. Mattsson, O. Isacson: Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation, Proc. Natl. Acad. Sci. USA 96, 12108–12113 (1999)

    Article  Google Scholar 

  70. H. Seo, A.W. Ferree, O. Isacson: Cortico-hippocampal APP and NGF levels are dynamically altered by cholinergic muscarinic antagonist or M1 agonist treatment in normal mice, Eur J. Neurosci. 15, 498–505 (2002)

    Article  Google Scholar 

  71. W. Liskowsky, R. Schliebs: Muscarinic acetylcholine receptor inhibition in transgenic Alzheimer-like Tg2576 mice by scopolamine favours the amyloidogenic route of processing of amyloid precursor protein, Int. J. Devl. Neurosci. 24, 149–156 (2006)

    Article  Google Scholar 

  72. A.A. Davis, J.J. Fritz, J. Wess, J.J. Lah, A.I. Levey: Deletion of M1 muscarinic acetylcholine receptors increases amyloid pathology in vitro and in vivo, J. Neurosci. 30, 4190–4196 (2010)

    Article  Google Scholar 

  73. A. Caccamo, S. Oddo, L.M. Billings, K.N. Green, H. Martinez-Coria, A. Fisher, F.M. LaFerla: M1 receptors play a central role in modulating AD-like pathology in transgenic mice, Neuron 49, 671–682 (2006)

    Article  Google Scholar 

  74. R. Medeiros, M. Kitazawa, A. Caccamo, D. Baglietto-Vargas, T. Estrada-Hernandez, D.H. Cribbs, A. Fisher, F.M. Laferla: Loss of muscarinic M(1) receptor exacerbates Alzheimerʼs disease-like pathology and cognitive decline, Am. J. Pathol. 179, 980–991 (2011)

    Article  Google Scholar 

  75. T. Züchner, J.R. Perez-Polo, R. Schliebs: β-secretase BACE1 is differentially controlled through muscarinic acetylcholine receptor signaling, J. Neurosci. Res. 77, 250–257 (2004)

    Article  Google Scholar 

  76. T.A. Kohout, R.J. Lefkowitz: Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization, Mol. Pharmacol. 63, 9–18 (2003)

    Article  Google Scholar 

  77. J. Liu, I. Rasul, Y. Sun, G. Wu, L. Li, R.T. Premont, W.Z. Suo: GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization, J. Biol. Chem. 284, 19564–19571 (2009)

    Article  Google Scholar 

  78. W. Zhang, A.S. Basile, J. Gomeza, L.A. Volpicelli, A.I. Levey, J. Wess: Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice, J. Neurosci. 22, 1709–1717 (2002)

    Google Scholar 

  79. Z. Suo, M. Wu, B.A. Citron, G.T. Wong, B.W. Festoff: Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimerʼs disease: An association with early beta-amyloid accumulation, J. Neurosci. 24, 3444–3452 (2004)

    Article  Google Scholar 

  80. S. Cheng, L. Li, S. He, J. Liu, Y. Sun, M. He, K. Grasing, R.T. Premont, W.Z. Suo: GRK5 deficiency accelerates β-amyloid accumulation in Tg2576 mice via impaired cholinergic activity, J. Biol. Chem. 285, 41541–41548 (2010)

    Article  Google Scholar 

  81. S. Efthimiopoulos, D. Vassilacopoulou, J.A. Ripellino, N. Tezapsidis, N.K. Robakis: Cholinergic agonists stimulate secretion of soluble full-length amyloid precursor protein in neuroendocrine cells, Proc. Natl. Acad. Sci. USA 93, 8046–8050 (1996)

    Article  Google Scholar 

  82. S.H. Kim, Y.K. Kim, S.J. Jeong, C. Haass, Y.H. Kim, Y.H. Suh: Enhanced release of secreted form of Alzheimerʼs amyloid precursor protein from PC12 cells by nicotine, Mol. Pharmacol. 52, 430–436 (1997)

    Google Scholar 

  83. J. Seo, S. Kim, H. Kim, C.H. Park, S. Jeong, J. Lee, S.H. Choi, K. Chang, J. Rah, J. Koo, E. Kim, Y. Suh: Effects of nicotine on APP secretion and Aβ- or CT(105)-induced toxicity, Biol. Psychiatry 49, 240–247 (2001)

    Article  Google Scholar 

  84. X.L. Qi, A. Nordberg, J. Xiu, Z.Z. Guan: The consequences of reducing expression of the alpha7 nicotinic receptor by RNA interference and of stimulating its activity with an alpha7 agonist in SH-SY5Y cells indicate that this receptor plays a neuroprotective role in connection with the pathogenesis of Alzheimerʼs disease, Neurochem. Int. 51, 377–383 (2007)

    Article  Google Scholar 

  85. T. Utsuki, M. Shoaib, H.W. Holloway, D.K. Ingram, W.C. Wallace, V. Haroutunian, K. Sambamurti, D.K. Lahiri, N.H. Greig: Nicotine lowers the secretion of the Alzheimerʼs amyloid β-protein precursor that contains amyloid β-peptide in rat, J. Alzheimers Dis. 4, 405–415 (2002)

    Google Scholar 

  86. D.K. Lahiri, T. Utsuki, D. Chen, M.R. Farlow, M. Shoaib, D.K. Ingram, N.H. Greig: Nicotine reduces the secretion of Alzheimerʼs β-amyloid precursor protein containing β-amyloid peptide in the rat without altering synaptic proteins, Ann. N. Y. Acad. Sci. 965, 364–372 (2002)

    Article  Google Scholar 

  87. M. Mousavi, E. Hellström-Lindahl: Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and decrease Abeta levels in vitro, Neurochem. Int. 54, 237–244 (2009)

    Article  Google Scholar 

  88. H.Z. Nie, S. Shi, R.J. Lukas, W.J. Zhao, Y.N. Sun, M. Yin: Activation of α7 nicotinic receptor affects APP processing by regulating secretase activity in SH-EP1-α7 nAChR-hAPP695 cells, Brain Res. 1356, 112–120 (2010)

    Article  Google Scholar 

  89. H.Z. Nie, Z.Q. Li, Q.X. Yan, Z.J. Wang, W.J. Zhao, L.C. Guo, M. Yin: Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4β2 nAChR-APP695 cells, Neurochem. Res. 36, 904–912 (2011)

    Article  Google Scholar 

  90. E. Hellstrom-Lindahl, J. Court, J. Keverne, M. Svedberg, M. Lee, A. Marutle, A. Thomas, E. Perry, I. Bednar, A. Nordberg: Nicotine reduces Aβ in the brain and cerebral vessels of APPsw mice, Eur. J. Neurosci. 19, 2703–2710 (2004)

    Article  Google Scholar 

  91. M. Srivareerat, T.T. Tran, S. Salim, A.M. Aleisa, K.A. Alkadhi: Chronic nicotine restores normal Aβ levels and prevents short-term memory and E-LTP impairment in Aβ rat model of Alzheimerʼs disease, Neurobiol. Aging 32, 834–844 (2011)

    Article  Google Scholar 

  92. J.A. Court, M. Johnson, D. Religa, J. Keverne, R. Kalaria, E. Jaros, I.G. McKeith, R. Perry, J. Naslund, E.K. Perry: Attenuation of Aβ deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking, Neuropathol. Appl. Neurobiol. 31, 522–535 (2005)

    Article  Google Scholar 

  93. A.M. Klein, N.W. Kowall, R.J. Ferrante: Neurotoxicity and oxidative damage of β-amyloid 1–42 versus β-amyloid 1–40 in the mouse cerebral cortex, Ann. N. Y. Acad. Sci. 893, 314–320 (1999)

    Article  Google Scholar 

  94. W. Härtig, A. Bauer, K. Brauer, J. Gosche, T. Hortobagyi, B. Penke, R. Schliebs, T. Harkany: Functional recovery of cholinergic basal forebrain neurons under disease conditions: Old problems, Rev. Neurosci. 13, 95–165 (2002)

    Article  Google Scholar 

  95. D.M. Walsh, D.J. Selkoe: Aβ oligomers – a decade of discovery, J. Neurochem. 101, 1172–1184 (2007)

    Article  Google Scholar 

  96. B.A. Yankner, T. Lu: Amyloid β-protein toxicity and the pathogenesis of Alzheimer disease, J. Biol. Chem. 284, 4755–4759 (2009)

    Article  Google Scholar 

  97. R. Schliebs, T. Arendt: The cholinergic system in aging and neuronal degeneration, Behav. Brain Res. 221, 555–563 (2011)

    Article  Google Scholar 

  98. T. Ondrejcak, I. Klyubin, N.W. Hu, A.E. Barry, W.K. Cullen, M.J. Rowan: Alzheimerʼs disease amyloid beta-protein and synaptic function, Neuromolecular Med. 12, 13–26 (2010)

    Article  Google Scholar 

  99. M.S. Parihar, G.J. Brewer: Amyloid beta as a modulator of synaptic plasticity, J. Alzheimers Dis. 22, 741–763 (2010)

    Google Scholar 

  100. J.P. Cleary, D.M. Walsh, J.J. Hofmeister, G.M. Shankar, M.A. Kuskowski, D.J. Selkoe, K.H. Ashe: Natural oligomers of the amyloid-β protein specifically disrupt cognitive function, Nat. Neurosci. 8, 79–84 (2005)

    Article  Google Scholar 

  101. S. Lesné, M.T. Koh, L. Kotinilek, R. Kayed, C.G. Glabe, A. Yang, M. Gallagher, K.H. Ashe: A specific amyloid protein assembly in the brain impairs memory, Nature 440, 352–357 (2006)

    Article  Google Scholar 

  102. C.A. McLean, R.A. Cherny, F.W. Fraser, S.J. Fuller, M.J. Smith, K. Beyreuther, A.I. Bush, C.L. Masters: Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimerʼs disease, Ann. Neurol. 46, 860–866 (1999)

    Article  Google Scholar 

  103. J. Apelt, A. Kumar, R. Schliebs: Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish mutation of human beta-amyloid precursor protein, Brain Res. 953, 17–30 (2002)

    Article  Google Scholar 

  104. H.J. Lüth, J. Apelt, A. Ihunwo, R. Schliebs: Degeneration of β-amyloid-associated cholinergic structures in transgenic APPSW mice, Brain Res. 977, 16–22 (2003)

    Article  Google Scholar 

  105. M. Klingner, J. Apelt, A. Kumar, D. Sorger, O. Sabri, J. Steinbach, M. Scheunemann, R. Schliebs: Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with β-amyloid plaque pathology, Int. J. Devl. Neurosci. 21, 357–369 (2003)

    Article  Google Scholar 

  106. A. Bellucci, I. Luccarini, C. Scali, C. Prosperi, M.G. Giovannini, G. Pepeu, F. Casamenti: Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice, Neurobiol. Dis. 23, 260–272 (2006)

    Article  Google Scholar 

  107. D. Van Dam, B. Marescau, S. Engelborghs, T. Cremers, J. Mulder, M. Staufenbiel, P.P. De Deyn: Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models, Neurochem. Int. 46, 409–422 (2005)

    Article  Google Scholar 

  108. K.R. Bales, E.T. Tzavara, S. Wu, M.R. Wade, F.P. Bymaster, S.M. Paul, G.G. Nomikos: Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-Aβ antibody, J. Clin. Invest. 116, 825–832 (2006)

    Article  Google Scholar 

  109. E. Machová, J. Jakubík, P. Michal, M. Oksman, H. Iivonen, H. Tanila, V. Dolezal: Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice, Neurobiol. Aging. 29, 368–378 (2008)

    Article  Google Scholar 

  110. Y. Luo, B. Bolon, S. Kahn, B.D. Bennett, S. Babu-Khan, P. Denis, W. Fan, H. Kha, J. Zhang, Y. Gong, L. Martin, J.C. Louis, Q. Yan, W.G. Richards, M. Citron, R. Vassar: Mice deficient in BACE1, the Alzheimerʼs beta-secretase, have normal phenotype and abolished β-amyloid generation, Nat. Neurosci. 4, 231–232 (2001)

    Article  Google Scholar 

  111. M. Ohno, E.A. Sametsky, L.H. Younkin, H. Oakley, S.G. Younkin, M. Citron, R. Vassar, J.F. Disterhoft: BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimerʼs disease, Neuron. 41, 27–33 (2004)

    Article  Google Scholar 

  112. F. Bao, L. Wicklund, P.N. Lacor, W.L. Klein, A. Nordberg, A. Marutle: Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity, Neurobiol. Aging. 33, 825.e1–825.e13 (2012)

    Article  Google Scholar 

  113. C. Haass, D.J. Selkoe: Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide, Cell 75, 1039–1042 (1993)

    Article  Google Scholar 

  114. M. Shoji, T.E. Golde, J. Ghiso, T.T. Cheung, S. Estus, L.M. Shaffer, X.D. Cai, D.M. McKay, R. Tintner, B. Frangione: Production of the Alzheimer amyloid beta protein by normal proteolytic processing, Science 258, 126–129 (1992)

    Article  Google Scholar 

  115. S. Kar, S.P. Slowikowski, D. Westaway, H.T. Mount: Interactions between β-amyloid and central cholinergic neurons: Implications for Alzheimerʼs disease, J. Psychiatry Neurosci. 29, 427–441 (2004)

    Google Scholar 

  116. R.J. Wurtman: Choline metabolism as a basis for the selective vulnerability of cholinergic neurons, Trends Neurosci. 15, 117–122 (1992)

    Article  Google Scholar 

  117. C. Hock, A. Maddalena, A. Raschig, F. Muller-Spahn, G. Eschweiler, K. Hager, I. Heuser, H. Hampel, T. Muller-Thomsen, W. Oertel, M. Wienrich, A. Signorell, C. Gonzalez-Agosti, M. Hoshi, A. Takashima, M. Murayama, K. Yasutake, N. Yoshida, K. Ishiguro, T. Hoshino, K. Imahori: Nontoxic amyloid β peptide 1–42 suppresses acetylcholine synthesis. Possible role in cholinergic dysfunction in Alzheimerʼs disease, J. Biol. Chem. 272, 2038–2041 (1997)

    Article  Google Scholar 

  118. W.A. Pedersen, M.A. Kloczewiak, J.K. Blusztajn: Amyloid β-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain, Proc. Natl. Acad. Sci. USA 93, 8068–8071 (1996)

    Article  Google Scholar 

  119. D. Hicks, D. John, N.Z. Makova, Z. Henderson, N.N. Nalivaeva, A.J. Turner: Membrane targeting, J. Neurochem. 116, 742–746 (2011)

    Article  Google Scholar 

  120. J.F. Kelly, K. Furukawa, S.W. Barger, M.R. Rengen, R.J. Mark, E.M. Blanc, G.S. Roth, M.P. Mattson: Amyloid β-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons, Proc. Natl. Acad. Sci. USA 93, 6753–6758 (1996)

    Article  Google Scholar 

  121. B. Wang, L. Yang, Z. Wang, H. Zheng: Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter, Proc. Natl. Acad. Sci. USA 104, 14140–14145 (2007)

    Article  Google Scholar 

  122. J. Pavia, J. Alberch, I. Alvárez, A. Toledano, M.L. de Ceballos: Repeated intracerebroventricular administration of beta-amyloid (25–35) to rats decreases muscarinic receptors in cerebral cortex, Neurosci. Lett. 278, 69–72 (2000)

    Article  Google Scholar 

  123. A. Thathiah, B. De Strooper: G protein-coupled receptors, cholinergic dysfunction, and Aβ toxicity in Alzheimerʼs disease, Sci. Signal. 2(93), re8 (2009)

    Google Scholar 

  124. T. Chiba, M. Yamada, J. Sasabe, K. Terashita, M. Shimoda, M. Matsuoka, S. Aiso: Amyloid-β causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons, Mol. Psychiatry 14, 206–222 (2009)

    Article  Google Scholar 

  125. L. Burghaus, U. Schütz, U. Krempel, R.A. de Vos, E.N. Jansen Steur, A. Wevers, J. Lindstrom, H. Schröder: Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients, Mol. Brain Res. 76, 385–388 (2000)

    Article  Google Scholar 

  126. M. Mousavi, E. Hellström-Lindahl, Z.Z. Guan, K.R. Shan, R. Ravid, A. Nordberg: Protein and mRNA levels of nicotinic receptors in brain of tobacco using controls and patients with Alzheimerʼs disease, Neuroscience 122, 515–520 (2003)

    Article  Google Scholar 

  127. C.M. Martin-Ruiz, J.A. Court, E. Molnar, M. Lee, C. Gotti, A. Mamalaki, T. Tsouloufis, S. Tzartos, C. Ballard, R.H. Perry, E.K. Perry: Alpha4 but not alpha3 and alpha7 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimerʼs disease, J. Neurochem. 73, 1635–1640 (1999)

    Article  Google Scholar 

  128. A. Wevers, H. Schröder: Nicotinic acetylcholine receptors in Alzheimerʼs disease, J. Alzheimers Dis. 1, 207–219 (1999)

    Google Scholar 

  129. A. Nordberg: Nicotinic receptor abnormalities of Alzheimerʼs disease: Therapeutic implications, Biol. Psychiatry 49, 200–210 (2001)

    Article  Google Scholar 

  130. S.D. Buckingham, A.K. Jones, L.A. Brown, D.B. Sattelle: Nicotinic acetylcholine receptor signalling: Roles in Alzheimerʼs disease and amyloid neuroprotection, Pharmacol. Rev. 61, 39–61 (2009)

    Article  Google Scholar 

  131. S. Jürgensen, S. Ferreira: Nicotinic receptors, amaloid-β, and synaptic failure in Alzheimerʼs disease, J. Mol. Neurosci. 40, 221–229 (2010)

    Article  Google Scholar 

  132. R.G. Nagele, M.R. DʼAndrea, W.J. Anderson, H.Y. Wang: Intracellular accumulation of beta-amyloid (1–42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimerʼs disease, Neuroscience 110, 199–211 (2002)

    Article  Google Scholar 

  133. F.J. Barrantes, V. Borroni, S. Vallés: Neuronal nicotinic acetylcholine receptor-cholesterol crosstalk in Alzheimerʼs disease, FEBS Lett. 584, 1856–1863 (2010)

    Article  Google Scholar 

  134. Z.Z. Guan, H. Miao, J.Y. Tian, C. Unger, A. Nordberg, X. Zhang: Suppressed expression of nicotinic acetylcholine receptors by nanomolar β-amyloid peptides in PC12 cells, J. Neural Transm. 108, 1417–1433 (2001)

    Article  Google Scholar 

  135. Q. Liu, H. Kawai, D.K. Berg: β-amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons, Proc. Natl. Acad. Sci. USA 98, 4734–4739 (2001)

    Article  Google Scholar 

  136. K.A. Alkadhi, K.H. Alzoubi, M. Srivareerat, T.T. Tran: Elevation of BACE in an Aβ rat model of Alzheimerʼs disease: Exacerbation by chronic stress and prevention by nicotine, Int. J. Neuropsychopharmacol. 28, 1–11 (2011)

    Google Scholar 

  137. H.Y. Wang, D.H. Lee, M.R. DʼAndrea, P.A. Peterson, R.P. Shank, A.B. Reitz: β-Amyloid(1–42) binds to α7 nicotinic acetylcholine receptor with high affinity, Implications for Alzheimerʼs disease pathology, J. Biol. Chem. 275, 5626–5632 (2000)

    Article  Google Scholar 

  138. H.Y. Wang, D.H. Lee, C.B. Davis, R.P. Shank: Amyloid peptide Aβ (1–42) binds selectively and with picomolar affinity to α7 nicotinic acetylcholine receptors, J. Neurochem. 75, 1155–1161 (2000)

    Article  Google Scholar 

  139. S. Oddo, A. Caccamo, K.N. Green, K. Liang, L. Tran, Y. Chen, F.M. Leslie, F.M. LaFerla: Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimerʼs disease, Proc. Natl. Acad. Sci. USA 102, 3046–3051 (2005)

    Article  Google Scholar 

  140. X.L. Qi, J. Xiu, K.R. Shan, Y. Xiao, R. Gu, R.Y. Liu, Z.Z. Guan: Oxidative stress induced by β-amyloid peptide (1–42) is involved in the altered composition of cellular membrane lipids and the decreased expression of nicotinic receptors in human SH-SY5Y neuroblastoma cells, Neurochem. Int. 46, 613–621 (2005)

    Article  Google Scholar 

  141. Z.Z. Guan, W.F. Yu, K.R. Shan, T. Nordman, J. Olsson, A. Nordberg: Loss of nicotinic receptors induced by β-amyloid peptides in PC12 cells: Possible mechanism involving lipid peroxidation, J. Neurosci. Res. 71, 397–406 (2003)

    Article  Google Scholar 

  142. K.T. Dineley, M. Westerman, D. Bui, K. Bell, K.H. Ashe, J.D. Sweatt: β-amyloid activates the mitogen-activated protein kinase cascade via hippocampal α7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimerʼs disease, J. Neurosci. 21, 4125–4133 (2001)

    Google Scholar 

  143. H.Y. Wang, W. Li, N.J. Benedetti, D.H. Lee: α7 nicotinic acetylcholine receptors mediate β-amyloid peptide-induced tau protein phosphorylation, J. Biol. Chem. 278, 31547–31553 (2003)

    Article  Google Scholar 

  144. K.T. Dineley, K.A. Bell, D. Bui, J.D. Sweatt: β-Amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes, J. Biol. Chem. 277, 25056–25061 (2002)

    Article  Google Scholar 

  145. M. Bencherif, P. Lippiello: α7 neuronal nicotinic receptors: The missing link to understanding Alzheimerʼs etiopathology?, Med. Hypotheses 74, 281–285 (2010)

    Article  Google Scholar 

  146. M. Hu, J.F. Waring, M. Gopalakrishnan, J. Li: Role of GSK-3β activation and α7 nAChRs in Aβ 1–42-induced tau phosphorylation in PC12 cells, J. Neurochem. 106, 1371–1377 (2008)

    Article  Google Scholar 

  147. G. Dziewczapolski, C.M. Glogowski, E. Masliah, S.F. Heinemann: Deletion of the α7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimerʼs disease, J. Neurosci. 29, 8805–8815 (2009)

    Article  Google Scholar 

  148. A.M. Lilja, O. Porras, E. Storelli, A. Nordberg, A. Marutle: Functional interactions of fibrillar and oligomeric amyloid-β with alpha7 nicotinic receptors in Alzheimerʼs disease, J. Alzheimers Dis. 23, 335–347 (2011)

    Google Scholar 

  149. Y. An, X.L. Qi, J.J. Pei, Z. Tang, Y. Xiao, Z.Z. Guan: Amyloid precursor protein gene mutated at Swedish 670/671 sites in vitro induces changed expression of nicotinic acetylcholine receptors and neurotoxicity, Neurochem. Int. 57, 647–654 (2010)

    Article  Google Scholar 

  150. G. Niewiadomska, A. Mietelska-Porowska, M. Mazurkiewicz: The cholinergic system, nerve growth factor and the cytoskeleton, Behav. Brain Res. 221, 515–526 (2011)

    Article  Google Scholar 

  151. S. Capsoni, R. Brandi, I. Arisi, M. DʼOnofrio, A. Cattaneo: A dual mechanism linking NGF/proNGF imbalance and early inflammation to Alzheimerʼs disease neurodegeneration in the AD11 Anti-NGF mouse model, CNS Neurol. Disord. Drug Targets, 10, 635–647 (2011)

    Article  Google Scholar 

  152. A. Salehi, J.D. Delcroix, P.V. Belichenko, K. Zhan, C. Wu, J.S. Valletta, R. Takimoto-Kimura, A.M. Kleschevnikov, K. Sambamurti, P.P. Chung, W. Xia, A. Villar, W.A. Campbell, L.S. Kulnane, R.A. Nixon, B.T. Lamb, C.J. Epstein, G.B. Stokin, L.S. Goldstein, C. Mobley: Increased APP expression in a mouse model of Downʼs syndrome disrupts NGF transport and causes cholinergic neuron degeneration, Neuron 51, 29–42 (2006)

    Article  Google Scholar 

  153. J. Fombonne, S. Rabizadeh, S. Banwait, P. Mehlen, D.E. Bredesen: Selective vulnerability in Alzheimerʼs disease: Amyloid precursor protein and p75(NTR) interaction, Ann. Neurol. 65, 294–303 (2009)

    Article  Google Scholar 

  154. K.K. Teng, S. Felice, T. Kim, B.L. Hempstead: Understanding proneurotrophin actions: Recent advances and challenges, Dev. Neurobiol. 70, 350–359 (2010)

    Google Scholar 

  155. M. Fahnestock, G. Yu, M.D. Coughlin: ProNGF: A neurotrophic or an apoptotic molecule?, Prog. Brain Res. 146, 101–110 (2004)

    Article  Google Scholar 

  156. M.A. Bruno, W.C. Leon, G. Fragoso, W.E. Mushynski, G. Almazan, A.C. Cuello: Amyloid β-induced nerve growth factor dysmetabolism in Alzheimer disease, J. Neuropathol. Exp. Neurol. 68, 857–869 (2009)

    Article  Google Scholar 

  157. E.J. Coulson, L.M. May, A.M. Sykes, A.S. Hamlin: The role of the p75 neurotrophin receptor in choplinergic dysfunction in Alzheimerʼs disease, Neuroscientist 15, 317–322 (2009)

    Article  Google Scholar 

  158. C. Costantini, F. Rossi, E. Formaggio, R. Bernardoni, D. Cecconi, V. Della-Bianca: Characterization of the signaling pathway downstream p75 neurotrophin receptor involved in β-amyloid peptide-dependent cell death, J. Mol. Neurosci. 25, 141–156 (2005)

    Article  Google Scholar 

  159. E.J. Coulson: Does the p75 neurotrophin receptor mediate Aβ-induced toxicity in Alzheimerʼs disease?, J. Neurochem. 98, 654–660 (2006)

    Article  Google Scholar 

  160. A. Sotthibundhu, A.M. Sykes, B. Fox, C.K. Underwood, W. Thangnipon, E.J. Coulson: β-Amyloid1–42 induces neuronal death through the p75 neurotrophin receptor, J. Neurosci. 28, 3941–3946 (2008)

    Article  Google Scholar 

  161. J.K. Knowles, J. Rajadas, T.V. Nguyen, T. Yang, M.C. LeMieux, L. Vander Griend, C. Ishikawa, S.M. Massa, T. Wyss-Coray, F.M. Longo: The p75 neurotrophin receptor promotes amyloid-beta (1–42)-induced neuritic dystrophy in vitro and in vivo, J. Neurosci. 29, 10627–10637 (2009)

    Article  Google Scholar 

  162. M. Yaar, S. Zhai, I. Panova, R.E. Fine, P.B. Eisenhauer, J.K. Blusztajn, I. Lopez-Coviella, B.A. Gilchrest: A cyclic peptide that binds p75(NTR) protects neurones from β amyloid (1–40)-induced cell death, Neuropathol. Appl. Neurobiol. 33, 533–543 (2007)

    Google Scholar 

  163. Y.J. Wang, X. Wang, J.J. Lu, Q.X. Li, C.Y. Gao, X.H. Liu, Y. Sun, M. Yang, Y. Lim, G. Evin, J.H. Zhong, C. Masters, X.F. Zhou: p75NTR regulates Aβ deposition by increasing Aβ production but inhibiting Aβ aggregation with its extracellular domain, J. Neurosci. 31, 2292–2304 (2011)

    Article  Google Scholar 

  164. B. Chakravarthy, C. Gaudet, M. Ménard, T. Atkinson, L. Brown, F.M. Laferla, U. Armato, J. Whitfield: Amyloid-β peptides stimulate the expression of the p75(NTR) neurotrophin receptor in SHSY5Y human neuroblastoma cells and AD transgenic mice, J. Alzheimers Dis. 19, 915–925 (2010)

    Google Scholar 

  165. M. Goedert, R. Jakes: Mutations causing neurodegenerative tauopathies, Biochim. Biophys. Acta 1739, 240–250 (2005)

    Article  Google Scholar 

  166. S. Oddo, A. Caccamo, M. Kitazawa, B.P. Tseng, F.M. LaFerla: Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimerʼs disease, Neurobiol. Aging 24, 1063–1070 (2003)

    Article  Google Scholar 

  167. L.M. Billings, S. Oddo, K.N. Green, J.L. McGaugh, F.M. LaFerla: Intraneuronal Aβ causes the onset of early Alzheimerʼs disease-related cognitive deficits in transgenic mice, Neuron 45, 675–688 (2005)

    Article  Google Scholar 

  168. M. Kitazawa, S. Oddo, T.R. Yamasaki, K.N. Green, F.M. LaFerla: Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimerʼs disease, J. Neurosci. 25, 8843–8853 (2005)

    Article  Google Scholar 

  169. S.D. Ginsberg, S. Che, S.E. Counts, E.J. Mufson: Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimerʼs disease, J. Neurochem. 96, 1401–1408 (2006)

    Article  Google Scholar 

  170. M. Mesulam: The cholinergic lesion of Alzheimerʼs disease: Pivotal factor or side show, Learn Mem. 11, 43–49 (2004)

    Article  Google Scholar 

  171. C. Geula, N. Nagykery, A. Nicholas, C.K. Wu: Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease, J. Neuropathol. Exp. Neurol. 67, 309–318 (2008)

    Article  Google Scholar 

  172. K. Belarbi, S. Burnouf, F.J. Fernandez-Gomez, J. Desmerciéres, L. Troquier, J. Brouillette, L. Tsambou, M.E. Grosjean, R. Caillierez, D. Demeyer, M. Hamdane, K. Schindowski, D. Blum, L. Buée: Loss of medial septum cholinergic neurons in THY-tau22 mouse model: What links with tau pathology?, Curr. Alzheimer Res. 8, 633–638 (2011)

    Article  Google Scholar 

  173. J.C. de la Torre: Vascular risk factor detection and control may prevent Alzheimerʼs disease, Ageing Res. Rev. 9, 218–225 (2010)

    Article  Google Scholar 

  174. C. Iadecola, L. Park, C. Capone: Threats to the mind: Aging, amyloid, and hypertension, Stroke. 40(3 Suppl), S40–44 (2009)

    Article  Google Scholar 

  175. J.C. de la Torre, T. Mussivand: Can disturbed brain microcirculation cause Alzheimerʼs disease?, Neurol. Res. 15, 146–153 (1993)

    Google Scholar 

  176. R.N. Kalaria: Vascular basis for brain degeneration: Faltering controls and risk factors for dementia, Nutr. Rev. 68(Suppl.), S74–87 (2010)

    Article  Google Scholar 

  177. N. Nicolakakis, E. Hamel: Neurovascular function in Alzheimerʼs disease patients and experimental models, Cereb. Blood Flow Metab. 31, 1354–1370 (2011)

    Article  Google Scholar 

  178. R.O. Weller, D. Boche, J.A.R. Nicoll: Microvasculature changes and cerebral amyloid angiopathy in Alzheimerʼs disease and their potential impact on therapy, Acta Neuropathol. 119, 87–102 (2009)

    Article  Google Scholar 

  179. C. Cordonnier, W.M. van der Flier: Brain microbleeds and Alzheimerʼs disease: Innocent observation or key player?, Brain 134, 335–344 (2011)

    Article  Google Scholar 

  180. B.V. Zlokovic: New therapeutic targets in the neurovascular pathway in Alzheimerʼs disease, Neurotherapeutics 5, 409–414 (2008)

    Article  Google Scholar 

  181. C.A. Hawkes, W. Härtig, J. Kacza, R. Schliebs, R.O. Weller, J.A. Nicoll, R.O. Carare: Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy, Acta Neuropathol. 121, 431–443 (2011)

    Article  Google Scholar 

  182. M. Merlini, E.P. Meyer, A. Ulmann-Schuler, R.M. Nitsch: Vascular β-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAβ mice, Acta Neuropathol. 122, 293–311 (2011)

    Article  Google Scholar 

  183. D. Paris, J. Humphrey, A. Quadros, N. Patel, R. Crescentini, F. Crawford, M. Mullan: Vasoactive effects of Aβ in isolated human cerebrovessels and in a transgenic mouse model of Alzheimerʼs disease: Role of inflammation, Neurol. Res. 25, 642–651 (2003)

    Article  Google Scholar 

  184. C. Iadecola: Neurovascular regulation in the normal brain and in Alzheimerʼs disease, Nat Rev. Neurosci. 5, 347–360 (2004)

    Article  Google Scholar 

  185. A. Rocchi, D. Orsucci, G. Tognoni, R. Ceravolo, G. Siciliano: The role of vascular factors in late-onset sporadic Alzheimerʼs disease. Genetic and molecular aspects, Curr. Alzheimer Res. 6, 224–237 (2009)

    Article  Google Scholar 

  186. H.J. Milionis, M. Florentin, S. Giannopoulos: Metabolic syndrome and Alzheimerʼs disease: A link to a vascular hypothesis?, CNS Spectrums 13, 606–613 (2008)

    Google Scholar 

  187. D.A. Snowdon, L.H. Greiner, J.A. Mortimer, K.P. Riley, P.A. Greiner, W.R. Markesbery: Brain infarction and the clinical expression of Alzheimer disease, The Nun Study, J. Am. Med. Assoc. 277, 813–817 (1997)

    Article  Google Scholar 

  188. S.L. Cole, R. Vassar: Linking vascular disorders and Alzheimerʼs disease: Potential involvement of BACE1, Neurbiol. Aging 30, 1535–1544 (2009)

    Article  Google Scholar 

  189. E.E. Smith, S.M. Greenberg: β-amyloid, blood vessels and brain function, Stroke 40, 2601–2606 (2009)

    Article  Google Scholar 

  190. H.K. Shin, P.B. Jones, M. Garcia-Alloza, L. Borrelli, S.M. Greenberg, B.J. Bacskai, M.P. Frosch, B.T. Hyman, M.A. Moskowitz, C. Ayata: Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy, Brain. 130(Pt 9), 2310–2319 (2007)

    Article  Google Scholar 

  191. D. Paris, N. Patel, A. DelleDonne, A. Quadros, R. Smeed, M. Mullan: Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis, Neurosci. Lett. 366, 80–85 (2004)

    Article  Google Scholar 

  192. D. Paris, K. Townsend, A. Quadros, J. Humphrey, J. Sun, S. Brem, M. Wotoczek-Obadia, A. DelleDonne, N. Patel, D.F. Obregon, R. Crescentini, L. Abdullah, D. Coppola, A.M. Rojiani, F. Crawford, S.M. Sebti, M. Mullan: Inhibition of angiogenesis by Aβ peptides, Angiogenesis 7, 75–85 (2004)

    Article  Google Scholar 

  193. C. Ruiz de Almodovar, D. Lambrechts, M. Mazzone, P. Carmeliet: Role and therapeutic potential of VEGF in the nervous system, Physiol. Rev. 89, 607–648 (2009)

    Article  Google Scholar 

  194. F.Y. Sun, X. Guo: Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor, J. Neurosci. Res. 79, 180–184 (2005)

    Article  Google Scholar 

  195. N. Ferrara, H.P. Gerber, J. LeCouter: The biology of VEGF and its receptors, Nat. Med. 9, 669–676 (2003)

    Article  Google Scholar 

  196. R.N. Kalaria, D.L. Cohen, D.R. Premkumar, S. Nag, J.C. LaManna, W.D. Lust: Vascular endothelial growth factor in Alzheimerʼs disease and experimental cerebral ischemia, Mol. Brain Res. 62, 101–105 (1998)

    Article  Google Scholar 

  197. E. Tarkowski, R. Issa, M. Sjogren, A. Wallin, K. Blennow, A. Tarkowski: Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimerʼs disease and vascular dementia, Neurobiol. Aging 23, 237–243 (2002)

    Article  Google Scholar 

  198. S.P. Yang, D.G. Bae, H.J. Kang, B.J. Gwag, Y.S. Gho, C.B. Chae: Co-accumulation of vascular endothelial growth factor with β-amyloid in the brain of patients with Alzheimerʼs disease, Neurobiol. Aging 25, 283–290 (2004)

    Article  Google Scholar 

  199. J.K. Ryu, T. Cho, H.B. Choi, Y.T. Wang, J.G. McLarnon: Microglial VEGF receptor response is an integral chemotactic component in Alzheimerʼs disease pathology, J. Neurosci. 29, 3–13 (2009)

    Article  Google Scholar 

  200. A.I. Pogue, W.J. Lukiw: Angiogenic signaling in Alzheimerʼs disease, Neuroreport 15, 1507–1510 (2004)

    Article  Google Scholar 

  201. L. Thirumangalakudi, P.G. Samany, A. Owoso, B. Wiskar, P. Grammas: Angiogenic proteins are expressed by brain blood vessels in Alzheimerʼs disease, J. Alzheimer Dis. 10, 111–118 (2006)

    Google Scholar 

  202. A.H. Vagnucci, W.W. Li: Alzheimerʼs disease and angiogenesis, Lancet 361, 605–608 (2003)

    Article  Google Scholar 

  203. B.S. Desai, J.A. Schneider, J.L. Li, P.M. Carvey, B. Hendey: Evidence of angiogenic vessels in Alzheimerʼs disease, J. Neural Transm. 116, 587–597 (2009)

    Article  Google Scholar 

  204. H.J. Marti, M. Bernaudin, A. Bellail, H. Schoch, M. Euler, W. Petit: Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia, Am. J. Pathol. 156, 965–976 (2000)

    Article  Google Scholar 

  205. I. Stein, M. Neeman, D. Shweiki, A. Itin, E. Keshet: Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes, Mol. Cell Biol. 15, 5363–5368 (1995)

    Article  Google Scholar 

  206. G.D. Yancopoulos, S. Davis, N.W. Gale, J.S. Rudge, S.J. Wiegand, J. Holash: Vascular-specific growth factors and blood vessel formation, Nature 407, 242–248 (2000)

    Article  Google Scholar 

  207. D. Paris, A. Quadros, N. Patel, A. DelleDonne, J. Humphrey, M. Mullan: Inhibition of angiogenesis and tumour growth by β- and γ-secretase inhibitors, Eur. J. Pharmacol. 514, 1–15 (2005)

    Article  Google Scholar 

  208. J.R. Ciallella, H. Figueiredo, V. Smith-Swintosky, J.P. McGillis: Thrombin induces surface and intracellular secretion of amyloid precursor protein from human endothelial cells, Thromb. Haemost. 81, 630–637 (1999)

    Google Scholar 

  209. S. Bürger, M. Noack, L.P. Kirazov, E.P. Kirazov, C.L. Naydenov, E. Kouznetsova, Y. Yafai, R. Schliebs: Vascular endothelial growth factor (VEGF) affects processing of the amyloid precursor protein and β-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain, Int. J. Dev. Neurosci. 27, 517–523 (2009)

    Article  Google Scholar 

  210. S. Bürger, Y. Yafai, M. Bigl, P. Wiedemann, R. Schliebs: Effect of VEGF and its receptor antagonist SU-5416, an inhibitor of angiogenesis, on processing of the β-amyloid precursor protein in primary neuronal cells derived from brain tissue of Tg2576 mice, Int. J. Dev. Neurosci. 28, 597–604 (2010)

    Article  Google Scholar 

  211. H. Girouard, C. Iadecola: Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease, J. Appl. Physiol. 100, 328–335 (2006)

    Article  Google Scholar 

  212. E. Hamel: Perivascular nerves and the regulation of cerebrovascular tone, J. Appl. Physiol. 100, 1059–1064 (2006)

    Article  Google Scholar 

  213. A.H. VanBeek, J.A. Claassen: The cerebrovascular role of the cholinergic neural system in Alzheimerʼs disease, Behav. Brain Res. 221, 537–542 (2003)

    Article  Google Scholar 

  214. E. Vaucher, E. Hamel: Cholinergic basal forebrain neurons project to cortical microvessels in the rat: Electron microscopic study with anterogradely transported Phaseolus vulgaris leucoagglutinin and choline acetyltransferase immunocytochemistry, J. Neurosci. 15, 7427–7441 (1995)

    Google Scholar 

  215. E. Hamel: Cholinergic modulation of the cortical microvascular bed, Prog. Brain Res. 145, 171–178 (2004)

    Article  Google Scholar 

  216. A. Elhusseiny, E. Hamel: Muscarinic–but not nicotinic–acetylcholine receptors mediate a nitric oxide-dependent dilation in brain cortical arterioles: A possible role for the M5 receptor subtype, J. Cereb. Blood Flow Metab. 20, 298–305 (2000)

    Article  Google Scholar 

  217. E. Farkas, P.G. Luiten: Cerebral microvascular pathology in aging and Alzheimerʼs disease, Prog. Neurobiol. 64, 575–611 (2001)

    Article  Google Scholar 

  218. B. Cauli, X.K. Tong, A. Rancillac, N. Serluca, B. Lambolez, J. Rossier, E. Hamel: Cortical GABA interneurons in neurovascular coupling: Relays for subcortical vasoactive pathways, J. Neurosci. 24, 8940–8949 (2004)

    Article  Google Scholar 

  219. C. Humpel, J. Marksteiner: Cerebrovascular damage as a cause for Alzheimerʼs disease, Curr. Neurovasc. Res. 2, 341–347 (2005)

    Article  Google Scholar 

  220. J.A. Claassen, R.W. Jansen: Cholinergically mediated augmentation of cerebral perfusion in Alzheimerʼs disease and related cognitive disorders: The cholinergic-vascular hypothesis, J. Gerontol. A Biol. Sci. Med. Sci. 61, 267–271 (2006)

    Article  Google Scholar 

  221. E. Kouznetsova, R. Schliebs: Role of cholinergic system in β-amyloid related changes of perivascular innervation of cerebral microvessels in transgenic Tg2576 Alzheimer-like mice, J. Neurochem. 101(Suppl. 1), 63 (2007)

    Google Scholar 

  222. A. Szutowicz, H. Bielarczyk, S. Gul, P. Zieliński, T. Pawełczyk, M. Tomaszewicz: Nerve growth factor and acetyl-l-carnitine evoked shifts in acetyl-CoA and cholinergic SN56 cell Vulnerability to neurotoxic inputs, J. Neurosci. Res. 79, 185–192 (2005)

    Article  Google Scholar 

  223. S.C. Correia, R.X. Santos, G. Perry, X. Zhu, P.I. Moreira, M.A. Smith: Insulin-resistant brain state: The culprit in sporadic Alzheimerʼs disease?, Ageing Res. Rev. 10, 264–273 (2011)

    Article  Google Scholar 

  224. M. Bigl, J. Apelt, K. Eschrich, R. Schliebs: Cortical glucose metabolism is altered in aged transgenic Tg2576 mice that demonstrate Alzheimer plaque pathology, J. Neural Transm. 110, 77–94 (2003)

    Google Scholar 

  225. P. Ghosh, A. Kumar, B. Datta, V. Rangachari: Dynamics of protofibril elongation and association involved in Aβ42 peptide aggregation in Alzheimerʼs disease, BMC Bioinformatics 11(Suppl 6), S24 (2010)

    Article  Google Scholar 

  226. N.L. Fawzi, E.H. Yap, Y. Okabe, K.L. Kohlstedt, S.P. Brown, T. Head-Gordon: Contrasting disease and nondisease protein aggregation by molecular simulation, Acc. Chem. Res. 41, 1037–1047 (2008)

    Article  Google Scholar 

  227. A.R. George, D.R. Howlett: Computationally derived structural models of the beta-amyloid found in Alzheimerʼs disease plaques and the interaction with possible aggregation inhibitors, Biopolymers 50, 733–741 (1999)

    Article  Google Scholar 

  228. S.Y. Ponomarev, J. Audie: Computational prediction and analysis of the DR6-NAPP interaction, Proteins. 79, 1376–1395 (2011)

    Article  Google Scholar 

  229. J. Luo, J.D. Maréchal, S. Wärmländer, A. Gräslund, A. Perálvarez-Marín: In silico analysis of the apolipoprotein E and the amyloid beta peptide interaction: Misfolding induced by frustration of the salt bridge network, PLoS Comput. Biol. 6(2), e1000663 (2010)

    Article  Google Scholar 

  230. J.Y. Chen, E. Youn, S.D. Mooney: Connecting protein interaction data, mutations, Methods Mol. Biol. 541, 449–461 (2009)

    Article  Google Scholar 

  231. K.C. Chou, K.D. Watenpaugh, R.L. Heinrikson: A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator, Biochem. Biophys. Res. Commun. 259, 420–428 (1999)

    Article  Google Scholar 

  232. Y. Huang, X. Sun, G. Hu: An integrated genetics approach for identifying protein signal pathways of Alzheimerʼs disease, Comput. Methods Biomech. Biomed. Engin. 14, 371–378 (2011)

    Article  Google Scholar 

  233. D.L. Cook, J.C. Wiley, J.H. Gennari: Chalkboard: Ontology-based pathway modeling and qualitative inference of disease mechanisms, Pac. Symp. Biocomput. 2007, 16–27 (2007)

    Google Scholar 

  234. I. García, Y. Fall, G. Gómez, H. González-Díaz: First computational chemistry multi-target model for anti-Alzheimer, anti-parasitic, anti-fungi, and anti-bacterial activity of GSK-3 inhibitors in vitro, in vivo, and in different cellular lines, Mol. Divers. 15, 561–567 (2011)

    Article  Google Scholar 

  235. R. Gómez-Balderas, D.F. Raffa, G.A. Rickard, P. Brunelle, A. Rauk: Computational studies of Cu(II)/Met and Cu(I)/Met binding motifs relevant for the chemistry of Alzheimerʼs disease, J. Phys. Chem. A 109, 5498–5508 (2005)

    Article  Google Scholar 

  236. R. Singh, A. Barman, R. Prabhakar: Computational insights into aspartyl protease activity of presenilin 1 (PS1) generating Alzheimer amyloid β-peptides (Aβ40 and Aβ42), J. Phys. Chem. B. 113, 2990–2999 (2009)

    Article  Google Scholar 

  237. M. Eisenstein: Genetics: Finding risk factors, Nature 475, S20–S22 (2011)

    Article  Google Scholar 

  238. M.D. Ritchie, L.W. Hahn, J.H. Moore: Power of multifactor dimensionality reduction for detecting gene–gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity, Genet. Epidemiol. 24, 150–157 (2003)

    Article  Google Scholar 

  239. S.Y. Lee, Y. Chung, R.C. Elston, Y. Kim, T. Park: Log-linear model-based multifactor dimensionality reduction method to detect gene gene interactions, Bioinformatics. 23, 2589–2595 (2007)

    Article  Google Scholar 

  240. J. Andrade, M. Andersen, A. Sillén, C. Graff, J. Odeberg: The use of grid computing to drive data-intensive genetic research, Eur. J. Hum. Genet. 15, 694–702 (2007)

    Article  Google Scholar 

  241. B. Liu, T. Jiang, S. Ma, H. Zhao, J. Li, X. Jiang, J. Zhang: Exploring candidate genes for human brain diseases from a brain-specific gene network, Biochem. Biophys. Res. Commun. 349, 1308–1314 (2006)

    Article  Google Scholar 

  242. K. Heinitz, M. Beck, R. Schliebs, J.R. Perez-Polo: Toxicity mediated by soluble oligomers of β-amyloid (1–42) on cholinergic SN56.B5.G4 cells, J. Neurochem. 98, 1930–1945 (2006)

    Article  Google Scholar 

  243. S. Joerchel, M. Raap, M. Bigl, K. Eschrich, R. Schliebs: Oligomeric β-amyloid (1–42) induces the expression of Alzheimer disease-relevant proteins in cholinergic SN56.B5.G4 cells as revealed by proteomic analysis, Int. J. Dev. Neurosci. 26, 301–308 (2006)

    Article  Google Scholar 

  244. J. Li, X. Zhu, J.Y. Chen: Building disease-specific drug-protein connectivity maps from molecular interaction networks and PubMed abstracts, PLoS Comput. Biol. 5(7), e1000450 (2009)

    Article  Google Scholar 

  245. Y. He, Z. Chen, G. Gong, A. Evans: Neuronal networks in Alzheimerʼs disease, Neuroscientist 15, 333–350 (2009)

    Article  Google Scholar 

  246. D.J. Watts, S.H. Strogatz: Collective dynamics of `small-worldʼ networks, Nature 393, 440–442 (1998)

    Article  Google Scholar 

  247. C.J. Stam, B.F. Jones, G. Nolte, M. Breakspear, P. Scheltens: Small-world networks and functional connectivity in Alzheimerʼs disease, Cereb. Cortex 17, 92–99 (2007)

    Article  Google Scholar 

  248. R. Tandon, S. Adak, J.A. Kaye: Neural networks for longitudinal studies in Alzheimerʼs disease, Artif. Intell. Med. 36, 245–255 (2006)

    Article  Google Scholar 

  249. M.E. Hasselmo: A computational model of the progression of Alzheimerʼs disease, M.D. Computing 14, 181–191 (1997)

    Google Scholar 

  250. M.E. Hasselmo: Neuromodulation and cortical function: Modeling the physiological basis of behavior, Behav. Brain Res. 67, 1–27 (1995)

    Article  Google Scholar 

  251. D. Horn, N. Levy, E. Ruppin: Neuronal-based synaptic compensation: A computational study in Alzheimerʼs disease, Neural Comput. 8, 1227–1243 (1996)

    Article  Google Scholar 

  252. L. Nickels, B. Biedermann, M. Coltheart, S. Saunders, J.J. Tree: Computational modelling of phonological dyslexia: How does the DRC model fare?, Cogn. Neuropsychol. 25, 165–193 (2008)

    Article  Google Scholar 

  253. A. Serna, V. Rialle, H. Pigot: Computational representation of Alzheimerʼs disease evolution applied to a cooking activity, Stud. Health Technol. Inform. 124, 587–592 (2006)

    Google Scholar 

  254. M.A. Ahmadi-Pajouh, F. Towhidkhah, S. Gharibzadeh, M. Mashhadimalek: Path planning in the hippocampo-prefrontal cortex pathway: An adaptive model based receding horizon planner, Med. Hypotheses 68, 1411–1415 (2007)

    Article  Google Scholar 

  255. E. Ruppin, J.A. Reggia: A neural model of memory impairment in diffuse cerebral atrophy, Br. J. Psychiatry. 166, 19–28 (1995)

    Article  Google Scholar 

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    Reinhard Schliebs

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Schliebs, R. (2014). Alzheimerʼs Disease. In: Kasabov, N. (eds) Springer Handbook of Bio-/Neuroinformatics. Springer Handbooks. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30574-0_51

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