title: [Genetics of late-onset Alzheimer's disease: vascular risk and beta-amyloid metabolism].
abstract: Progress in clinical and basic research of Alzheimer's disease (AD) suggested theoretical models of possible pathogenetic mechanisms, with a primary role of the genetic factors that have been implicated in AD. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial AD (presenilins 1 and 2, and amyloid beta protein precursor [APP]): well characterized but that account for only a small proportion of AD cases. Secondly, late onset, sporadic AD is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease: particularly, apolipoprotein E (apo E) polymorphism and many others suggested by linkage studies [alpha-macroglobulin, low density receptor protein (LRP1), bleomycin hydrolase], with a precise role in beta-amyloid metabolism and deposition. Many of these are controversial and studies have shown conflicting results, but apoE polymorphism seems to be only one of the possible genetic factors suggested to play a role in the multifactoral pathogenesis of AD. Regional and ethnic differences may affect the strength of association between apoE epsilon 4 allele and the disease, and we reported evidences of the decreasing frequency of epsilon 4 allele in AD patients and centenarians from Northern to Southern European regions. Finally, several genetic risk factors of vascular origin (angiotensin converting enzyme, methyltetrahydropholate-reductase, and NOS3 gene polymorphisms) have been implicated in the development of both vascular dementia and AD with conflicting results.
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000150:complications; D003327:Coronary Disease / Q000150:complications; D015140:Dementia, Vascular / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D036281:Genetic Research; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D011110:Polymorphism, Genetic; D053766:Presenilin-2; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2
vernacular_title: Genetica nell malattia di Alzheimer ad esordio tardivo: rischio vascolare e metabolismo della beta-amiloide.