Genetic variants in presenilins and correlation to amyloid-beta 42 levels in cerebrospinal fluid and diagnosis of Alzheimer's disease

Background: Aim of this study was to assess genetic variability in human presenilin 1 and 2 (PSEN) genes in Alzheimer's disease (AD) patients in relation to β-amyloid 42 (Aβ42) levels in cerebrospinal fluid (CSF) and clinical symptoms. We hypothesized that by specific phenotyping through biomarkers the chance of identifying novel disease-modifying genetic variations might be increased. Conclusions: While non-synonymous mutations of PSEN1 and PSEN2 were found only sporadically, haplotype analysis of PSEN2 revealed associations with the level of Aβ42 in early-onset and late-onset AD patients. The underrepresentation of haplotype 4/4 among AD patients and lack of β-amyloid deposits in brain autopsy samples from 4/4 carriers might point to a potentially protective effect of this haplotype on amyloid plaques formation.