Acta Biochimica Polonica · 2004 · 31 citations · 19 references
Life SciencesGeneticsMolecular GeneticsDementiaGenetic CounselingHuman GeneticsAlzheimer DiseaseGenetic DisordersNeurodegenerative Disease GeneticsNeurodegenerative DiseasesNeurodegenerative DisordersNeurogenetic DisordersAmyloid Beta PeptidesAmyloid FibrilsApp MutationsAutosomal Dominant InheritanceEarly Onset Alzheimer DiseaseFamilial DementiaFamilial Neurodegenerative DiseasePresenilin Mutations
A small number (1-5%) of Alzheimer's disease (AD) cases associated with the early-onset form of the disease (EOAD) appears to be transmitted as a pure genetic, autosomal dominant trait. To date, three genes responsible for familial EOAD have been identified in the human genome: amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutations in these genes account for a significant fraction (18 to 50%) of familial cases of early onset AD. The mutations affect APP processing causing increased production of the toxic Abeta42 peptide. According to the "amyloid cascade hypothesis", aggregation of the Abeta42 peptide in brain is a primary event in AD pathogenesis. In our study of twenty AD patients with a positive family history of dementia, 15% (3 of 20) of the cases could be explained by coding sequence mutations in the PS1 gene. Although a frequency of PS1 mutations is less than 2% in the whole population of AD patients, their detection has a significant diagnostic value for both genetic counseling and treatment in families with AD.
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Clinical diagnosis of Alzheimer's disease
Guy M. McKhann, David A. Drachman, Marshall Folstein et al. · Neurology · 1984 · 28K citations · Full text
Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus
Ephrat Levy‐Lahad, Wilma Wasco, Parvoneh Poorkaj et al. · Science · 1995 · 2.6K citations