[Advances in molecular biology and clinical study of amyloid precursor protein for Alzheimer's disease].
Alzheimer's disease (AD) is the most common cause of dementia in elderly population. There are two hallmark pathological lesions: the intracellular neurofibrillary tangles (NFTs) and the extracellular amyloid deposits in the senile plaques (SP). The NFTs are aggregates of hyperphosphorylated microtubule Tau protein. The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides-Abeta40 and Abeta42. The Abeta peptides are derived from the amyloid precursor protein (APP) which is considered very important for the AD pathogenesis. In recent years, studies have focused on understanding the generation of Abeta peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and progression of both familial and sporadic AD (FAD and SAD). This review covers the trafficking and processing of APP, the amyloid cascade hypothesis in AD pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset and late-onset AD. The risk factor apolipoprotein E (ApoE) for AD and therapeutic anti-beta-amyloid vaccination strategies for prevention of AD are also discussed.
Xu
Bao-gang
BG
Washington University School of Medicine, St.Louis, Mo 63110, USA.
Wu
Xun
X
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D023582:Alzheimer Vaccines / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D006801:Humans; D016233:Immunotherapy, Active; D008565:Membrane Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1; D053766:Presenilin-2
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2; C086839:amyloid beta-protein (17-42)