title: Molecular pathogenesis of sporadic and familial forms of Alzheimer's disease.
abstract: Our understanding of the pathogenesis of Alzheimer's disease (AD) comes primarily from the study of rare inherited forms of the disease. Mutations that cause familial AD appear to act by a common mechanism: that of increasing production of A beta 42/43, one of the family of A beta peptides deposited in senile plaques. However, increased A beta 42/43 production has not been demonstrated to occur in most cases of sporadic AD, suggesting that genetic and environmental factors acting at other stages of the disease process can modify the risk for disease. Such factors most likely include those affecting A beta aggregation or clearance, the inflammatory response, cerebrovascular disease, or susceptibility of neurons to injury. Identifying these factors will lead to a better understanding of the etiology of the disease and provide additional targets for therapeutic intervention.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. goate@icarus.wustl.edu
authors.forename: W J
authors.initials: WJ
authors.lastname: Ray
authors.forename: F
authors.initials: F
authors.lastname: Ashall
authors.forename: A M
authors.initials: AM
authors.lastname: Goate
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002091:Butyrylcholinesterase / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications; D004198:Disease Susceptibility; D005799:Genes, Dominant; D006801:Humans; D007249:Inflammation; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D009457:Neuroglia / Q000473:pathology; D009498:Neurotoxins / Q000009:adverse effects; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000737:chemistry; D053764:Presenilin-1; D053766:Presenilin-2; D012307:Risk Factors; D000514:alpha 1-Antichymotrypsin / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015415:Biomarkers; D008565:Membrane Proteins; D009498:Neurotoxins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D000514:alpha 1-Antichymotrypsin; D002091:Butyrylcholinesterase; D002118:Calcium