Has the amyloid cascade hypothesis for Alzheimer's disease been proved?
After much initial debate for and against the role of amyloid in Alzheimer's disease (AD), mutations on the amyloid precursor protein (APP) and processing pathways that increase levels of the amyloid b peptide of 42 residues (Abeta42) have established that faulty function or processing of these proteins are responsible for AD pathogenesis. Given the neurotoxicity of aggregates of Ab42, the central role of this peptide in AD pathogenesis is self evident. In this article, I summarize the major pieces of evidence adduced to support the amyloid cascade hypothesis and point out their limitations.
Hardy
John
J
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A1015, 35 Convent Drive, Room 1A1015 MSC 3707, Bethesda, MD 20892-3707, USA. hardyj@mail.nih.gov
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000682:Amyloid / Q000235:genetics / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000502:physiology / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics* / Q000633:toxicity; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins