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Molecular genetics of Alzheimer's disease
Author(s) -
Hardy J.
Publication year - 1996
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1996.tb05867.x
Subject(s) - alzheimer's disease , disease , degenerative disease , medicine , molecular genetics , genetics , neuroscience , psychology , biology , gene
Four genes have thus far been implicated in the etiology of Alzheimer's disease (AD). A series of mutations in the amyloid precursor protein (APP) gene on chromosome 21, which cause disease with a typical onset of 55 years of age, have been described. These include mutations at APP 670/671 , APP 692 , and APP 717 . The ε4 allele of the apolipoprotein E (ApoE) gene on chromosome 19 is positively associated with disease, whereas the ε2 allele is usually negatively associated with disease. Mutations in the S182 gene on chromosome 14 seem to cause disease with an onset age of <50 years and mutations in a gene on chromosome 1 (S182 Like Protein: S182LP) cause disease with variable onset. These genetic findings are reviewed within the framework of the amyloid cascade hypothesis of AD etiology and pathogenesis. The occurrence and effects of the mutations in APP and the fact that the ε4 allele of ApoE are genetic risk factors point to the hypothesis that the extracellular deposition of β‐amyloid is the key initiating event in the pathogenesis of AD.