Intraneuronal Aβ and Alzheimer’s Disease

  • Lauren M. Billings
  • Frank M. LaFerla
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 57)


Mild Cognitive Impairment Down Syndrome Amyloid Precursor Protein Inclusion Body Myositis Amyloid Precursor Protein Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Ritchie K, Lovestone S. The dementias. Lancet 2002;360:1759–1766.PubMedCrossRefGoogle Scholar
  2. 2.
    Albert MS. Cognitive and neurobiologic markers of early Alzheimer disease. Proc Natl Acad Sci U S A 1996;93:13547–13551.PubMedCrossRefGoogle Scholar
  3. 3.
    Grossberg GT. Diagnosis and treatment of Alzheimer's disease. J Clin Psychiatry 2003;64(suppl 9):3–6.PubMedGoogle Scholar
  4. 4.
    Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol 2004;61:59–66.PubMedCrossRefGoogle Scholar
  5. 5.
    Nicoll JA, Wilkinson D, Holmes C, et al. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003;9:448–452.PubMedCrossRefGoogle Scholar
  6. 6.
    Oddo S, Billings L, Kesslak JP, et al. Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 2004;43:321–332.PubMedCrossRefGoogle Scholar
  7. 7.
    Goedert M, Jakes R, Spillantini MG, et al. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 1996;383:550–553.PubMedCrossRefGoogle Scholar
  8. 8.
    Billings LM, Oddo S, Green KN, et al. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 2005;45:675–688.PubMedCrossRefGoogle Scholar
  9. 9.
    Clark CM, Xie S, Chittams J, et al. Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Arch Neurol 2003;60:1696–1702.PubMedCrossRefGoogle Scholar
  10. 10.
    Whitehouse PJ, Price DL, Struble RG, et al. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 1982;215:1237–1239.PubMedCrossRefGoogle Scholar
  11. 11.
    Masliah E. Mechanisms of synaptic pathology in Alzheimer's disease. J Neural Transm Suppl 1998;53:147–158.PubMedGoogle Scholar
  12. 12.
    Masliah E, Ellisman M, Carragher B, et al. Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease. J Neuropathol Exp Neurol 1992;51:404–414.PubMedCrossRefGoogle Scholar
  13. 13.
    Davis KL, Mohs RC, Marin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 1999;281:1401–1406.PubMedCrossRefGoogle Scholar
  14. 14.
    DeKosky ST, Ikonomovic MD, Styren SD, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002;51:145–155.PubMedCrossRefGoogle Scholar
  15. 15.
    Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991;349:704–706.PubMedCrossRefGoogle Scholar
  16. 16.
    Mullan M, Crawford F, Axelman K, et al. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet 1992;1:345–347.PubMedCrossRefGoogle Scholar
  17. 17.
    Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995;375:754–760.PubMedCrossRefGoogle Scholar
  18. 18.
    Levy-Lahad E, Wijsman EM, Nemens E, et al. A familial Alzheimer's disease locus on chromosome 1. Science 1995;269:970–973.PubMedCrossRefGoogle Scholar
  19. 19.
    Rogaev EI, Sherrington R, Rogaeva EA, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 1995;376:775–778.PubMedCrossRefGoogle Scholar
  20. 20.
    De Strooper B, Saftig P, Craessaerts K, et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 1998;391:387–390.PubMedCrossRefGoogle Scholar
  21. 21.
    Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993;261:921–923.PubMedCrossRefGoogle Scholar
  22. 22.
    Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998;43:815–825.PubMedCrossRefGoogle Scholar
  23. 23.
    Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998;393:702–705.PubMedCrossRefGoogle Scholar
  24. 24.
    Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002;297:353–356.PubMedCrossRefGoogle Scholar
  25. 25.
    Mucke L, Masliah E, Johnson WB, et al. Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. Brain Res 1994;666:151–167.PubMedCrossRefGoogle Scholar
  26. 26.
    Hsiao KK. Understanding the biology of beta-amyloid precursor proteins in transgenic mice. Neurobiol Aging 1995;16:705–706.PubMedCrossRefGoogle Scholar
  27. 27.
    Moechars D, Dewachter I, Lorent K, et al. Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 1999;274:6483–6492.PubMedCrossRefGoogle Scholar
  28. 28.
    Van Dam D, D'Hooge R, Staufenbiel M, et al. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 2003;17:388–396.PubMedCrossRefGoogle Scholar
  29. 29.
    LaFerla FM. Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat Rev Neurosci 2002;3:862–872.PubMedCrossRefGoogle Scholar
  30. 30.
    Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001;293:1491–1495.PubMedCrossRefGoogle Scholar
  31. 31.
    Lewis J, Dickson DW, Lin WL, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001;293:1487–1491.PubMedCrossRefGoogle Scholar
  32. 32.
    McKee AC, Kosik KS, Kowall NW. Neuritic pathology and dementia in Alzheimer's disease. Ann Neurol 1991;30:156–165.PubMedCrossRefGoogle Scholar
  33. 33.
    Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572–580.PubMedCrossRefGoogle Scholar
  34. 34.
    Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992;42:631–639.PubMedGoogle Scholar
  35. 35.
    Samuel W, Terry RD, DeTeresa R, et al. Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Arch Neurol 1994;51:772–778.PubMedGoogle Scholar
  36. 36.
    Janus C, Pearson J, McLaurin J, et al. A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 2000;408:979–982.PubMedCrossRefGoogle Scholar
  37. 37.
    Morgan D, Diamond DM, Gottschall PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000;408:982–985.PubMedCrossRefGoogle Scholar
  38. 38.
    Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci 2002;5:452–457.PubMedGoogle Scholar
  39. 39.
    Chen G, Chen KS, Knox J, et al. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature 2000;408:975–979.PubMedCrossRefGoogle Scholar
  40. 40.
    Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996;274:99–102.PubMedCrossRefGoogle Scholar
  41. 41.
    Gyure KA, Durham R, Stewart WF, et al. Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome. Arch Pathol Lab Med 2001;125:489–492.PubMedGoogle Scholar
  42. 42.
    Mor C, Spooner ET, Wisniewsk KE, et al. Intraneuronal Abeta42 accumulation in Down syndrome brain. Amyloid 2002;9:88–102.Google Scholar
  43. 43.
    Wirths O, Multhaup G, Czech C, et al. Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett 2001;306:116–120.PubMedCrossRefGoogle Scholar
  44. 44.
    Wirths O, Multhaup G, Czech C, et al. Intraneuronal APP/A beta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice. Brain Pathol 2002;12:275–286.PubMedCrossRefGoogle Scholar
  45. 45.
    Tabira T, Chui DH, Kuroda S. Significance of intracellular Abeta42 accumulation in Alzheimer's disease. Front Biosci 2002;7:a44–a49.PubMedCrossRefGoogle Scholar
  46. 46.
    Takahashi RH, Almeida CG, Kearney PF, et al. Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci 2004;24:3592–3599.PubMedCrossRefGoogle Scholar
  47. 47.
    Takahashi RH, Milner TA, Li F, et al. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 2002;161:1869–1879.PubMedGoogle Scholar
  48. 48.
    Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003;39:409–421.PubMedCrossRefGoogle Scholar
  49. 49.
    Shie FS, LeBoeuf RC, Jin LW. Early intraneuronal Abeta deposition in the hippocampus of APP transgenic mice. Neuroreport 2003;14:123–129.PubMedCrossRefGoogle Scholar
  50. 50.
    Casas C, Sergeant N, Itier JM, et al. Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. Am J Pathol 2004;165:1289–1300.PubMedGoogle Scholar
  51. 51.
    Gouras GK, Tsai J, Naslund J, et al. Intraneuronal Abeta42 accumulation in human brain. Am J Pathol 2000;156:15–20.PubMedGoogle Scholar
  52. 52.
    Echeverria V, Ducatenzeiler A, Dowd E, et al. Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons. Neuroscience 2004;129:583–592.PubMedCrossRefGoogle Scholar
  53. 53.
    LaFerl, FM, Tinkle BT, Bieberich CJ, et al. The Alzheimer's A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nat Genet 1995;9:21–30.CrossRefGoogle Scholar
  54. 54.
    Magrane J, Smith RC, Walsh K, Querfurth HW. Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons. J Neurosci 2004;24:1700–1706.PubMedCrossRefGoogle Scholar
  55. 55.
    Zhang Y, McLaughlin R, Goodyer C, LeBlanc A. Selective cytotoxicity of intracellular amyloid beta peptide1-42 through p53 and Bax in cultured primary human neurons. J Cell Biol 2002;156:519–529.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Lauren M. Billings
    • 1
  • Frank M. LaFerla
  1. 1.Department of Neurobiology and BehaviorUniversity of CaliforniaIrvineUSA

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