Genetics of Alzheimer's disease.
Mutations in any one of three genes can cause autosomal dominant, early-onset Alzheimer's disease: these genes are the amyloid precursor protein (APP) gene on chromosome 21, the presenilin-1 (PS-1) gene on chromosome 14 and the presenilin-2 (PS-2) gene on chromosome 1. Pathogenic mutations at all these loci cause mismetabolism of APP such that more of the peptide A beta 42 is produced. This peptide is deposited in the plaques in the brains of Alzheimer's patients. These facts have led to the dominant hypothesis for the disease process: the 'amyloid cascade hypothesis', which proposes that overproduction or failure to clear the peptide A beta 42 is always central to the disease. Genetic variability at the apoliprotein E locus is a major determinant of late onset Alzheimer's disease. The mechanism by which apoliprotein E is involved in the pathogenesis of Alzheimer's disease is not yet known. There are likely to be other genetic factors which impinge on Alzheimer's disease.
Hutton
M
M
Neurogenetics Laboratory, Mayo Clinic Jacksonville, FL 32224, USA.
Pérez-Tur
J
J
Hardy
J
J
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D005799:Genes, Dominant; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D053764:Presenilin-1; D053766:Presenilin-2; D012307:Risk Factors
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; C075222:amyloid beta-protein (1-42)