title: The genetics of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the major cause of dementia in the U.K. The clinical diagnosis of the specific disease resulting in dementia is unreliable and thus a definitive diagnosis of AD is best made in conjunction with post-mortem findings of amyloid plaques and neurofibrillary tangles. Alzheimer's disease is neuropathologically indistinguishable in the young and old, but has been divided arbitrarily into early- and late-onset disease using age cut-offs of 60 or 65 years. Twin and family studies suggest that genetic factors play a major role in its aetiology. This review considers the three loci which have been shown to be associated with early-onset AD: amyloid precursor protein, presenilin (PS)-1 and PS-2. Mutations in these genes seem to be associated with overproduction of the 42-amino acid form of beta-amyloid, suggesting that this may be a central pathological process in AD. The impact of the different apo E alleles on the risks for late- and early-onset AD is discussed and compared with other dementing conditions. Recent analyses suggest that there are likely to be other genes besides apo E which impact on late-onset AD risk. The possible roles in AD of the mitochondrial mutation at position 4336, the PS intron 8 polymorphism, and variants in the alpha 1-antichymotrypsin and VLDL-receptor genes, are considered.
authors.affiliation: Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: D C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D003704:Dementia / Q000235:genetics; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D053764:Presenilin-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1