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Neurobiological Mechanisms Involved in the Pathogenesis of Alzheimer’s Disease

  • Fayaz Ahmad Mir
  • Zaigham Abbas RizviEmail author
Chapter

Abstract

Alzheimer’s disease (AD) is one of the many neurodegenerative disorders which is characterized by progressive loss of neurons due to the extracellular accumulation of misprocessed and aggregated amyloid beta (Aβ)-plaques and appearance of intracellular neurofibrillary tangles containing hyperphosphorylated tau protein which ultimately leads to loss of synapses and cognitive decline. Aggregation of amyloid beta (Aβ)-plaques is the hallmark of AD. Aβ is the proteolytic cleavage product of amyloid precursor protein (APP) which is cleaved by β- and γ-secretase enzymes into Aβ1–42 and Aβ1–40 isoforms where the former readily aggregate more rapidly than the latter. Tau protein, the major component of neurofibrillary tangles, is a microtubule-associated protein which is usually soluble but becomes insoluble as it forms tangles of oligomers which is thought to be initiated by toxic concentrations of Aβ-plaques. Recent studies have shown that some genetic mutations, genomic instability and other factors like head injuries, depression, imbalanced diet and age progression all contribute to the development and progression of AD. The most important gene, for which a role in ageing-related late-onset AD has been established since a decade, is APOE where different variants of the gene differently predispose the individuals to the development of AD. In this chapter, we will be highlighting well-established molecular and cellular mechanisms behind the development and progression of AD, the regions in the brain that are affected and the known genetic basis behind the onset and pathophysiology of AD. In the later section, we will address some of the current and prospective therapeutic interventions based on our current understanding of neurobiological mechanisms underlying AD.

Keywords

Alzheimer’s disease Aβ-plaques Neurodegeneration Cytotoxicity Neuroinflammation tau protein Axonal transport 

References

  1. Ansari MA et al (2006) In vivo administration of D609 leads to protection of subsequently isolated gerbil brain mitochondria subjected to in vitro oxidative stress induced by amyloid beta-peptide and other oxidative stressors: relevance to Alzheimer’s disease and other oxidative stress-related neurodegenerative disorders. Free Radic Biol Med 41(11):1694–1703PubMedPubMedCentralCrossRefGoogle Scholar
  2. Association, A.s (2018) 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 14(3):367–429CrossRefGoogle Scholar
  3. Atwood CS et al (2003) Amyloid-beta: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta. Brain Res Brain Res Rev 43(1):1–16PubMedCrossRefPubMedCentralGoogle Scholar
  4. Avila J et al (2004) Role of tau protein in both physiological and pathological conditions. Physiol Rev 84(2):361–384PubMedCrossRefPubMedCentralGoogle Scholar
  5. Baas PW, Qiang L (2005) Neuronal microtubules: when the MAP is the roadblock. Trends Cell Biol 15(4):183–187PubMedCrossRefPubMedCentralGoogle Scholar
  6. Baloh RH et al (2007) Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci 27(2):422–430PubMedPubMedCentralCrossRefGoogle Scholar
  7. Baudier J, Cole RD (1988) Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II. J Biol Chem 263(12):5876–5883PubMedGoogle Scholar
  8. Block ML (2008) NADPH oxidase as a therapeutic target in Alzheimer’s disease. BMC Neurosci 9(Suppl 2):S8PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bobinski M et al (1996) Neurofibrillary pathology–correlation with hippocampal formation atrophy in Alzheimer disease. Neurobiol Aging 17(6):909–919PubMedGoogle Scholar
  10. Bonda DJ et al (2010) Mitochondrial dynamics in Alzheimer’s disease: opportunities for future treatment strategies. Drugs Aging 27(3):181–192PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bowman AB et al (1999) Drosophila roadblock and Chlamydomonas LC7: a conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis. J Cell Biol 146(1):165–180PubMedPubMedCentralCrossRefGoogle Scholar
  12. Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 121(2):171–181PubMedCrossRefGoogle Scholar
  13. Brown A (2003) Axonal transport of membranous and nonmembranous cargoes: a unified perspective. J Cell Biol 160(6):817–821PubMedPubMedCentralCrossRefGoogle Scholar
  14. Buee L et al (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33(1):95–130PubMedCrossRefGoogle Scholar
  15. Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J Neurosci 18(8):2801–2807PubMedCrossRefGoogle Scholar
  16. Butterfield DA, Boyd-Kimball D (2018) Oxidative stress, amyloid-β peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer’s disease. J Alzheimers Dis 62(3):1345–1367PubMedPubMedCentralCrossRefGoogle Scholar
  17. Butterfield SM, Lashuel HA (2010) Amyloidogenic protein–membrane interactions: mechanistic insight from model systems. Angew Chem Int Ed 49(33):5628–5654CrossRefGoogle Scholar
  18. Butterfield DA et al (2001) Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 7(12):548–554PubMedCrossRefGoogle Scholar
  19. Butterfield DA et al (2006) Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer’s disease. Neurobiol Dis 22(2):223–232PubMedCrossRefGoogle Scholar
  20. Butterfield DA et al (2007) Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radic Biol Med 43(5):658–677PubMedPubMedCentralCrossRefGoogle Scholar
  21. Butterfield DA, Swomley AM, Sultana R (2013) Amyloid β-peptide (1–42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19(8):823–835PubMedPubMedCentralCrossRefGoogle Scholar
  22. Canevari L, Clark JB, Bates TE (1999) β-Amyloid fragment 25–35 selectively decreases complex IV activity in isolated mitochondria. FEBS Lett 457(1):131–134PubMedCrossRefGoogle Scholar
  23. Carrillo-Mora P, Luna R, Colin-Barenque L (2014) Amyloid beta: multiple mechanisms of toxicity and only some protective effects? Oxidative Med Cell Longev 2014:795375CrossRefGoogle Scholar
  24. Cash AD et al (2003) Microtubule reduction in Alzheimer’s disease and aging is independent of tau filament formation. Am J Pathol 162(5):1623–1627PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cassagnes L-E et al (2013) The catalytically active copper-amyloid-Beta state: coordination site responsible for reactive oxygen species production. Angew Chem Int Ed 52(42):11110–11113CrossRefGoogle Scholar
  26. Castegna A et al (2004) Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: implications for Alzheimer’s disease. Brain Res 1004(1–2):193–197PubMedCrossRefGoogle Scholar
  27. Chalermpalanupap T et al (2013) Targeting norepinephrine in mild cognitive impairment and Alzheimer’s disease. Alzheimers Res Ther 5(2):21PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chang KA, Suh YH (2010) Possible roles of amyloid intracellular domain of amyloid precursor protein. BMB Rep 43(10):656–663PubMedCrossRefGoogle Scholar
  29. Cheignon C et al (2018) Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 14:450–464CrossRefGoogle Scholar
  30. Chen Y et al (2016) Mitochondrial DNA rearrangement Spectrum in brain tissue of Alzheimer’s disease: analysis of 13 cases. PLoS One 11(6):e0154582PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chow VW et al (2010) An overview of APP processing enzymes and products. NeuroMolecular Med 12(1):1–12PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cui JG et al (2007) Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer’s disease. Neuroreport 18(2):115–119PubMedCrossRefPubMedCentralGoogle Scholar
  33. de Paula VDJR et al (2009) Neurobiological pathways to Alzheimer’s disease: Amyloid-beta, TAU protein or both? Dementia & Neuropsychologia 3(3):188–194CrossRefGoogle Scholar
  34. Decker H et al (2010) Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons. J Neurosci 30(27):9166–9171PubMedPubMedCentralCrossRefGoogle Scholar
  35. Duering M et al (2005) Mean age of onset in familial Alzheimer’s disease is determined by amyloid beta 42. Neurobiol Aging 26(6):785–788PubMedCrossRefPubMedCentralGoogle Scholar
  36. Duff K et al (1996) Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383(6602):710–713PubMedCrossRefPubMedCentralGoogle Scholar
  37. Ebbing B et al (2008) Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum Mol Genet 17(9):1245–1252PubMedCrossRefPubMedCentralGoogle Scholar
  38. Eckert A et al (2010) Convergence of amyloid-beta and tau pathologies on mitochondria in vivo. Mol Neurobiol 41(2–3):107–114PubMedPubMedCentralCrossRefGoogle Scholar
  39. Eckman CB, Eckman EA (2007) An update on the amyloid hypothesis. Neurol Clin 25(3):669–682PubMedPubMedCentralCrossRefGoogle Scholar
  40. Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Asp Med 29(5):258–289CrossRefGoogle Scholar
  41. Farrer MJ et al (2009) DCTN1 mutations in Perry syndrome. Nat Genet 41(2):163–165PubMedPubMedCentralCrossRefGoogle Scholar
  42. Ferreira A, Caceres A, Kosik KS (1993) Intraneuronal compartments of the amyloid precursor protein. J Neurosci 13(7):3112–3123PubMedCrossRefGoogle Scholar
  43. Gao HM et al (2002) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 81(6):1285–1297PubMedCrossRefGoogle Scholar
  44. García-Escudero V et al (2013) Deconstructing mitochondrial dysfunction in Alzheimer disease. Oxidative Med Cell Longev 2013:13, Article Id 162152Google Scholar
  45. German DC et al (1992) Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32(5):667–676PubMedCrossRefGoogle Scholar
  46. Gibson GE et al (2012) Deficits in the mitochondrial enzyme α-ketoglutarate dehydrogenase lead to Alzheimer’s disease-like calcium dysregulation. Neurobiology of aging 33(6):1121.e13–1121.e24CrossRefGoogle Scholar
  47. Glabe CC (2005) Amyloid accumulation and pathogenesis of Alzheimer’s disease: significance of monomeric, oligomeric and fibrillar Abeta. Subcell Biochem 38:167–177PubMedCrossRefGoogle Scholar
  48. Godoy JA et al (2014) Signaling pathway cross talk in Alzheimer’s disease. Cell Commun Signal 12(1):23PubMedPubMedCentralCrossRefGoogle Scholar
  49. Goldstein LS, Yang Z (2000) Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu Rev Neurosci 23:39–71PubMedCrossRefGoogle Scholar
  50. Gong CX, Grundke-Iqbal I, Iqbal K (1994) Dephosphorylation of Alzheimer’s disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience 61(4):765–772PubMedCrossRefPubMedCentralGoogle Scholar
  51. Gouras GK et al (1998) Generation and regulation of beta-amyloid peptide variants by neurons. J Neurochem 71(5):1920–1925PubMedCrossRefPubMedCentralGoogle Scholar
  52. Grimm M, Hartmann T (2012) Recent understanding of the molecular mechanisms of Alzheimer’s disease. J Addict Res Ther 5:1–27Google Scholar
  53. Grudzien A et al (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 28(3):327–335PubMedCrossRefPubMedCentralGoogle Scholar
  54. Grundke-Iqbal I et al (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83(13):4913–4917PubMedPubMedCentralCrossRefGoogle Scholar
  55. Gunawardena S, Goldstein LS (2001) Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32(3):389–401CrossRefGoogle Scholar
  56. Gunawardena S, Goldstein LS (2004) Cargo-carrying motor vehicles on the neuronal highway: transport pathways and neurodegenerative disease. J Neurobiol 58(2):258–271PubMedCrossRefPubMedCentralGoogle Scholar
  57. Gupta A, Goyal R (2016) Amyloid beta plaque: a culprit for neurodegeneration. Acta Neurol Belg 116(4):445–450PubMedCrossRefPubMedCentralGoogle Scholar
  58. Hanger DP, Seereeram A, Noble W (2009) Mediators of tau phosphorylation in the pathogenesis of Alzheimer’s disease. Expert Rev Neurother 9(11):1647–1666PubMedCrossRefPubMedCentralGoogle Scholar
  59. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388PubMedCrossRefPubMedCentralGoogle Scholar
  60. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedPubMedCentralCrossRefGoogle Scholar
  61. Heneka MT et al (2010) Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci U S A 107(13):6058–6063PubMedPubMedCentralCrossRefGoogle Scholar
  62. Herzog AG, Kemper TL (1980) Amygdaloid changes in aging and dementia. Arch Neurol 37(10):625–629PubMedCrossRefGoogle Scholar
  63. Higuchi M, Lee VM, Trojanowski JQ (2002) Tau and axonopathy in neurodegenerative disorders. NeuroMolecular Med 2(2):131–150PubMedCrossRefGoogle Scholar
  64. Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279(5350):519–526PubMedCrossRefPubMedCentralGoogle Scholar
  65. Hiruma H et al (2003) Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J Neurosci 23(26):8967–8977PubMedPubMedCentralCrossRefGoogle Scholar
  66. Hodgkin AL, Huxley AF (1939) Action potentials recorded from inside a nerve fibre. Nature 144:710CrossRefGoogle Scholar
  67. Huang X et al (1999) Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274(52):37111–37116PubMedCrossRefPubMedCentralGoogle Scholar
  68. Ito S et al (2007) Cerebral clearance of human amyloid-β peptide (1–40) across the blood–brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes. J Neurochem 103(6):2482–2490PubMedCrossRefPubMedCentralGoogle Scholar
  69. Ittner LM et al (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 142(3):387–397PubMedCrossRefPubMedCentralGoogle Scholar
  70. Jeynes B, Provias J (2008) Evidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis. Curr Alzheimer Res 5(5):432–437PubMedCrossRefGoogle Scholar
  71. Jobst KA et al (1992) Detection in life of confirmed Alzheimer’s disease using a simple measurement of medial temporal lobe atrophy by computed tomography. Lancet 340(8829):1179–1183PubMedCrossRefGoogle Scholar
  72. Jobst KA et al (1994) Rapidly progressing atrophy of medial temporal lobe in Alzheimer’s disease. Lancet 343(8901):829–830PubMedCrossRefGoogle Scholar
  73. Jomova K et al (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345(1–2):91–104PubMedCrossRefGoogle Scholar
  74. Kamal A et al (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414(6864):643–648PubMedCrossRefGoogle Scholar
  75. Kayed R et al (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300(5618):486–489CrossRefGoogle Scholar
  76. Kelleher RJ 3rd, Shen J (2017) Presenilin-1 mutations and Alzheimer’s disease. Proc Natl Acad Sci U S A 114(4):629–631PubMedPubMedCentralCrossRefGoogle Scholar
  77. Ko SY et al (2015) The possible mechanism of advanced Glycation end products (AGEs) for Alzheimer’s disease. PLoS One 10(11):e0143345PubMedPubMedCentralCrossRefGoogle Scholar
  78. Koo EH et al (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci U S A 87(4):1561–1565PubMedPubMedCentralCrossRefGoogle Scholar
  79. Kowalska A (2004) Genetic aspects of amyloid beta-protein fibrillogenesis in Alzheimer’s disease. Folia Neuropathol 42(4):235–237PubMedGoogle Scholar
  80. Lal R, Lin H, Quist AP (2007) Amyloid beta ion channel: 3D structure and relevance to amyloid channel paradigm. Biochim Biophys Acta 1768(8):1966–1975PubMedPubMedCentralCrossRefGoogle Scholar
  81. Lee VM, Daughenbaugh R, Trojanowski JQ (1994) Microtubule stabilizing drugs for the treatment of Alzheimer’s disease. Neurobiol Aging 15(Suppl 2):S87–S89PubMedCrossRefGoogle Scholar
  82. Lee M-C et al (2018) Zinc ion rapidly induces toxic, off-pathway amyloid-β oligomers distinct from amyloid-β derived diffusible ligands in Alzheimer’s disease. Sci Rep 8(1):4772PubMedPubMedCentralCrossRefGoogle Scholar
  83. Li Y et al (2012) Analysis of hippocampal gene expression profile of Alzheimer’s disease model rats using genome chip bioinformatics. Neural Regen Res 7(5):332–340PubMedPubMedCentralGoogle Scholar
  84. Liang WS et al (2008) Altered neuronal gene expression in brain regions differentially affected by Alzheimer’s disease: a reference data set. Physiol Genomics 33(2):240–256PubMedPubMedCentralCrossRefGoogle Scholar
  85. Lin H, Bhatia R, Lal R (2001) Amyloid β protein forms ion channels: implications for Alzheimer’s disease pathophysiology. FASEB J 15(13):2433–2444PubMedCrossRefGoogle Scholar
  86. Lindwall G, Cole RD (1984) Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem 259(8):5301–5305PubMedGoogle Scholar
  87. Liu F et al (2002) Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS Lett 512(1–3):101–106PubMedCrossRefGoogle Scholar
  88. Lloret A et al (2011) Amyloid-beta toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer’s disease. J Alzheimers Dis 27(4):701–709PubMedPubMedCentralCrossRefGoogle Scholar
  89. Lopez-Toledano MA, Shelanski ML (2004) Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. J Neurosci 24(23):5439–5444PubMedPubMedCentralCrossRefGoogle Scholar
  90. Luo Y et al (2003) BACE1 (β-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol Dis 14(1):81–88PubMedCrossRefGoogle Scholar
  91. Luxenberg JS et al (1987) Rate of ventricular enlargement in dementia of the Alzheimer type correlates with rate of neuropsychological deterioration. Neurology 37(7):1135–1140PubMedCrossRefGoogle Scholar
  92. Magistretti PJ, Allaman I (2015) A cellular perspective on brain energy metabolism and functional imaging. Neuron 86(4):883–901PubMedCrossRefGoogle Scholar
  93. Magrane J et al (2005) Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J Neurosci 25(47):10960–10969PubMedPubMedCentralCrossRefGoogle Scholar
  94. Mark RJ et al (1997) A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem 68(1):255–264PubMedCrossRefGoogle Scholar
  95. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23(1):134–147PubMedPubMedCentralCrossRefGoogle Scholar
  96. Martin M et al (1999) Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport. Mol Biol Cell 10(11):3717–3728PubMedPubMedCentralCrossRefGoogle Scholar
  97. Matsuda S et al (2001) c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer’s amyloid precursor protein with JNK. J Neurosci 21(17):6597–6607PubMedPubMedCentralCrossRefGoogle Scholar
  98. Matthews FE et al (2013) A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet (London, England) 382(9902):1405–1412CrossRefGoogle Scholar
  99. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60(5):748–766PubMedPubMedCentralCrossRefGoogle Scholar
  100. Mc Donald JM et al (2015) The aqueous phase of Alzheimer’s disease brain contains assemblies built from approximately 4 and approximately 7 kDa Abeta species. Alzheimers Dement 11(11):1286–1305PubMedPubMedCentralCrossRefGoogle Scholar
  101. McInnes J (2013) Insights on altered mitochondrial function and dynamics in the pathogenesis of neurodegeneration. Transl Neurodegener 2(1):12PubMedPubMedCentralCrossRefGoogle Scholar
  102. Meda L et al (1995) Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374(6523):647–650PubMedCrossRefGoogle Scholar
  103. Miller KR, Streit WJ (2007) The effects of aging, injury and disease on microglial function: a case for cellular senescence. Neuron Glia Biol 3(3):245–253PubMedCrossRefGoogle Scholar
  104. Miller DL et al (1993) Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer’s disease. Arch Biochem Biophys 301(1):41–52PubMedCrossRefGoogle Scholar
  105. Misko A et al (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30(12):4232–4240PubMedPubMedCentralCrossRefGoogle Scholar
  106. Montoliu-Gaya L, Villegas S (2015) Protein structures in Alzheimer’s disease: the basis for rationale therapeutic design. Arch Biochem Biophys 588:1–14PubMedCrossRefGoogle Scholar
  107. Moreira PI (2018) Sweet mitochondria: a shortcut to Alzheimer’s disease. J Alzheimers Dis 62(3):1391–1401PubMedPubMedCentralCrossRefGoogle Scholar
  108. Morfini G et al (2002) Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J 21(3):281–293PubMedPubMedCentralCrossRefGoogle Scholar
  109. Morfini GA et al (2009) Axonal transport defects in neurodegenerative diseases. J Neurosci 29(41):12776–12786PubMedPubMedCentralCrossRefGoogle Scholar
  110. Mudher A, Lovestone S (2002) Alzheimer’s disease-do tauists and baptists finally shake hands? Trends Neurosci 25(1):22–26PubMedCrossRefPubMedCentralGoogle Scholar
  111. Muresan Z, Muresan V (2005) Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1. J Cell Biol 171(4):615–625PubMedPubMedCentralCrossRefGoogle Scholar
  112. Newsway V et al (2010) Perry syndrome due to the DCTN1 G71R mutation – a distinctive L-DOPA responsive disorder with behavioural syndrome, vertical gaze palsy and respiratory failure. Mov Disord 25(6):767–770PubMedPubMedCentralCrossRefGoogle Scholar
  113. Noble W et al (2003) Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38(4):555–565PubMedCrossRefGoogle Scholar
  114. Nunomura A et al (2009) RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 118(1):151–166PubMedCrossRefGoogle Scholar
  115. O’Nuallain B et al (2010) Amyloid β-protein dimers rapidly form stable Synaptotoxic Protofibrils. J Neurosci 30(43):14411–14419PubMedPubMedCentralCrossRefGoogle Scholar
  116. Ohshima Y et al (2018) Mutations in the β-amyloid precursor protein in familial Alzheimer’s disease increase Aβ oligomer production in cellular models. Heliyon 4(1):e00511–e00511PubMedPubMedCentralCrossRefGoogle Scholar
  117. Omar RA et al (1999) Increased expression but reduced activity of antioxidant enzymes in Alzheimer’s disease. J Alzheimers Dis 1(3):139–145PubMedCrossRefPubMedCentralGoogle Scholar
  118. Perluigi M et al (2006a) In vivo protection by the xanthate tricyclodecan-9-yl-xanthogenate against amyloid beta-peptide (1-42)-induced oxidative stress. Neuroscience 138(4):1161–1170PubMedCrossRefPubMedCentralGoogle Scholar
  119. Perluigi M et al (2006b) In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1-42-induced oxidative stress. J Neurosci Res 84(2):418–426PubMedCrossRefPubMedCentralGoogle Scholar
  120. Pietri M et al (2013) PDK1 decreases TACE-mediated alpha-secretase activity and promotes disease progression in prion and Alzheimer’s diseases. Nat Med 19(9):1124–1131PubMedCrossRefGoogle Scholar
  121. Pigino G et al (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci U S A 106(14):5907–5912PubMedPubMedCentralCrossRefGoogle Scholar
  122. Plant LD et al (2003) The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci 23(13):5531–5535PubMedPubMedCentralCrossRefGoogle Scholar
  123. Poulin SP et al (2011) Amygdala atrophy is prominent in early Alzheimer’s disease and relates to symptom severity. Psychiatry Res 194(1):7–13PubMedPubMedCentralCrossRefGoogle Scholar
  124. Premkumar DR et al (1995) Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer’s disease. J Neurochem 65(3):1399–1402PubMedCrossRefGoogle Scholar
  125. Prince M et al (2016) Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 8(1):23PubMedPubMedCentralCrossRefGoogle Scholar
  126. Puls I et al (2003) Mutant dynactin in motor neuron disease. Nat Genet 33(4):455–456PubMedCrossRefGoogle Scholar
  127. Qin L et al (2004) NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 279(2):1415–1421PubMedCrossRefGoogle Scholar
  128. Rajendran R et al (2009) A novel approach to the identification and quantitative elemental analysis of amyloid deposits—insights into the pathology of Alzheimer’s disease. Biochem Biophys Res Commun 382(1):91–95PubMedCrossRefGoogle Scholar
  129. Rissman RA et al (2004) Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. J Clin Invest 114(1):121–130PubMedPubMedCentralCrossRefGoogle Scholar
  130. Roher AE et al (1993) Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A 90(22):10836–10840PubMedPubMedCentralCrossRefGoogle Scholar
  131. Rosales-Corral S et al (2004a) Kinetics of the neuroinflammation-oxidative stress correlation in rat brain following the injection of fibrillar amyloid-β onto the hippocampus in vivo. J Neuroimmunol 150(1–2):20–28PubMedCrossRefPubMedCentralGoogle Scholar
  132. Rosales-Corral S et al (2004b) Kinetics of the neuroinflammation-oxidative stress correlation in rat brain following the injection of fibrillar amyloid-beta onto the hippocampus in vivo. J Neuroimmunol 150(1–2):20–28PubMedCrossRefPubMedCentralGoogle Scholar
  133. Rui Y et al (2006) Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci 26(41):10480–10487PubMedPubMedCentralCrossRefGoogle Scholar
  134. Sadigh-Eteghad S et al (2014) Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner. J Med Hypotheses Ideas 8(2):49–52CrossRefGoogle Scholar
  135. Sagare A et al (2007) Clearance of amyloid-β by circulating lipoprotein receptors. Nat Med 13:1029PubMedPubMedCentralCrossRefGoogle Scholar
  136. Satizabal CL et al (2016) Incidence of dementia over three decades in the Framingham heart study. N Engl J Med 374(6):523–532PubMedPubMedCentralCrossRefGoogle Scholar
  137. Scahill RI et al (2002) Mapping the evolution of regional atrophy in Alzheimer’s disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci U S A 99(7):4703–4707PubMedPubMedCentralCrossRefGoogle Scholar
  138. Schilling T, Eder C (2011) Amyloid-beta-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia. J Cell Physiol 226(12):3295–3302PubMedCrossRefPubMedCentralGoogle Scholar
  139. Scott SA, DeKosky ST, Scheff SW (1991) Volumetric atrophy of the amygdala in Alzheimer’s disease: quantitative serial reconstruction. Neurology 41(3):351–356PubMedCrossRefPubMedCentralGoogle Scholar
  140. Scott SA et al (1992) Amygdala cell loss and atrophy in Alzheimer’s disease. Ann Neurol 32(4):555–563PubMedCrossRefPubMedCentralGoogle Scholar
  141. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8(6):595–608PubMedPubMedCentralCrossRefGoogle Scholar
  142. Sengupta U, Nilson AN, Kayed R (2016) The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine 6:42–49PubMedPubMedCentralCrossRefGoogle Scholar
  143. Shankar GM et al (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14(8):837–842PubMedPubMedCentralCrossRefGoogle Scholar
  144. Sisodia SS, Tanzi RE (2007) Alzheimer’s disease: advances in genetics, molecular and cellular biology. Springer Science & Business Media, New YorkCrossRefGoogle Scholar
  145. Small DH, Mok SS, Bornstein JC (2001) Alzheimer’s disease and Abeta toxicity: from top to bottom. Nat Rev Neurosci 2(8):595–598PubMedCrossRefGoogle Scholar
  146. Smith AD (2002) Imaging the progression of Alzheimer pathology through the brain. Proc Natl Acad Sci 99(7):4135PubMedCrossRefGoogle Scholar
  147. Smith KDB et al (2007) In vivo axonal transport rates decrease in a mouse model of Alzheimer’s disease. NeuroImage 35(4):1401–1408PubMedPubMedCentralCrossRefGoogle Scholar
  148. St George-Hyslop PH, Petit A (2005) Molecular biology and genetics of Alzheimer’s disease. C R Biol 328(2):119–130PubMedCrossRefPubMedCentralGoogle Scholar
  149. Stancu IC et al (2014) Models of beta-amyloid induced Tau-pathology: the long and “folded” road to understand the mechanism. Mol Neurodegener 9:51PubMedPubMedCentralCrossRefGoogle Scholar
  150. Steenland K et al (2016) A meta-analysis of Alzheimer’s disease incidence and prevalence comparing African-Americans and Caucasians. J Alzheimers Dis 50(1):71–76PubMedPubMedCentralCrossRefGoogle Scholar
  151. Stokin GB et al (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307(5713):1282–1288PubMedCrossRefPubMedCentralGoogle Scholar
  152. Subramaniam R et al (1997) The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins. J Neurochem 69(3):1161–1169PubMedCrossRefPubMedCentralGoogle Scholar
  153. Sun X, Chen WD, Wang YD (2015a) beta-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol 6:221PubMedPubMedCentralGoogle Scholar
  154. Sun X, Chen W-D, Wang Y-D (2015b) β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol 6:221PubMedPubMedCentralGoogle Scholar
  155. Takashima A et al (1998) Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc Natl Acad Sci U S A 95(16):9637–9641PubMedPubMedCentralCrossRefGoogle Scholar
  156. Talmat-Amar Y, Arribat Y, Parmentier M-L (2018) Vesicular axonal transport is modified in vivo by Tau deletion or overexpression in Drosophila. Int J Mol Sci 19(3):744PubMedCentralCrossRefGoogle Scholar
  157. Tang Y et al (2012) Early and selective impairments in axonal transport kinetics of synaptic cargoes induced by soluble amyloid beta-protein oligomers. Traffic 13(5):681–693PubMedPubMedCentralCrossRefGoogle Scholar
  158. Tarrade A et al (2006) A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet 15(24):3544–3558PubMedCrossRefPubMedCentralGoogle Scholar
  159. Thal DR et al (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58(12):1791–1800CrossRefGoogle Scholar
  160. Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208PubMedCrossRefPubMedCentralGoogle Scholar
  161. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer’s patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21(13):4923–4930PubMedPubMedCentralCrossRefGoogle Scholar
  162. Varadarajan S et al (1999) Methionine residue 35 is important in amyloid beta-peptide-associated free radical oxidative stress. Brain Res Bull 50(2):133–141PubMedCrossRefPubMedCentralGoogle Scholar
  163. Varadarajan S et al (2001) Different mechanisms of oxidative stress and neurotoxicity for Alzheimer’s A beta(1–42) and A beta(25–35). J Am Chem Soc 123(24):5625–5631PubMedCrossRefPubMedCentralGoogle Scholar
  164. Vassar R et al (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286(5440):735–741PubMedCrossRefGoogle Scholar
  165. Verhey KJ et al (2001) Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol 152(5):959–970PubMedPubMedCentralCrossRefGoogle Scholar
  166. Vershinin M et al (2007) Multiple-motor based transport and its regulation by Tau. Proc Natl Acad Sci U S A 104(1):87–92PubMedCrossRefGoogle Scholar
  167. Vetrivel KS et al (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem 279(43):44945–44954PubMedPubMedCentralCrossRefGoogle Scholar
  168. Vetrivel KS et al (2005) Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem 280(27):25892–25900PubMedPubMedCentralCrossRefGoogle Scholar
  169. Vicario-Orri E, Opazo CM, Munoz FJ (2015) The pathophysiology of axonal transport in Alzheimer’s disease. J Alzheimers Dis 43(4):1097–1113PubMedCrossRefGoogle Scholar
  170. Violet M et al (2015) Prefibrillar Tau oligomers alter the nucleic acid protective function of Tau in hippocampal neurons in vivo. Neurobiol Dis 82:540–551PubMedCrossRefGoogle Scholar
  171. Vogt BA, Crino PB, Vogt LJ (1992) Reorganization of cingulate cortex in Alzheimer’s disease: neuron loss, neuritic plaques, and muscarinic receptor binding. Cereb Cortex 2(6):526–535PubMedCrossRefGoogle Scholar
  172. Walsh DM, Selkoe DJ (2007) A beta oligomers – a decade of discovery. J Neurochem 101(5):1172–1184PubMedPubMedCentralCrossRefGoogle Scholar
  173. Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17(1):5–21PubMedCrossRefPubMedCentralGoogle Scholar
  174. Wang X et al (2010) Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis 7(1–3):56–59PubMedPubMedCentralCrossRefGoogle Scholar
  175. Wang X et al (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta 1842(8):1240–1247CrossRefGoogle Scholar
  176. Wasco W et al (1993) Isolation and characterization of APLP2 encoding a homologue of the Alzheimer’s associated amyloid beta protein precursor. Nat Genet 5(1):95–100PubMedCrossRefGoogle Scholar
  177. Wildsmith KR et al (2013) Evidence for impaired amyloid beta clearance in Alzheimer’s disease. Alzheimers Res Ther 5(4):33PubMedPubMedCentralCrossRefGoogle Scholar
  178. Wilquet V, De Strooper B (2004) Amyloid-beta precursor protein processing in neurodegeneration. Curr Opin Neurobiol 14(5):582–588PubMedCrossRefGoogle Scholar
  179. Wirths O et al (2006) Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer’s disease. Acta Neuropathol 111(4):312–319PubMedCrossRefGoogle Scholar
  180. Wu DC et al (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci U S A 100(10):6145–6150PubMedPubMedCentralCrossRefGoogle Scholar
  181. Xu L-L et al (2017) Mitochondrial dynamics changes with age in an APPsw/PS1dE9 mouse model of Alzheimer’s disease. Neuroreport 28(4):222–228PubMedPubMedCentralCrossRefGoogle Scholar
  182. Xu F et al (2018) KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth. The Journal of Cell Biology 217:3480–3496PubMedPubMedCentralCrossRefGoogle Scholar
  183. Yagishita S (1978) Morphological investigations on axonal swellings and spheroids in various human diseases. Virchows Arch A Pathol Anat Histol 378(3):181–197PubMedCrossRefGoogle Scholar
  184. Yankner B, Duffy L, Kirschner D (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250(4978):279–282CrossRefGoogle Scholar
  185. Yatin SM, Aksenov M, Butterfield DA (1999) The antioxidant vitamin E modulates amyloid beta-peptide-induced creatine kinase activity inhibition and increased protein oxidation: implications for the free radical hypothesis of Alzheimer’s disease. Neurochem Res 24(3):427–435PubMedCrossRefGoogle Scholar
  186. Zarow C et al (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60(3):337–341PubMedCrossRefGoogle Scholar
  187. Zhang H et al (2012) Proteolytic processing of Alzheimer’s beta-amyloid precursor protein. J Neurochem 120(Suppl 1):9–21PubMedCrossRefGoogle Scholar
  188. Zhao C et al (2001) Charcot-Marie-tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105(5):587–597PubMedCrossRefGoogle Scholar
  189. Zhu N et al (2015) Huperzine A protects neural stem cells against Abeta-induced apoptosis in a neural stem cells and microglia co-culture system. Int J Clin Exp Pathol 8(6):6425–6433PubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Centre for Microbial EcologyTranslational Health Science and Technology Institute, NCR Biotech Science ClusterFaridabadIndia

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