Variable expression of presenilin 1 is not a major determinant of risk for late-onset Alzheimer's Disease

Abstract

We have previously reported a significant association between early-onset Alzheimer's disease (EOAD) and an allele in the promoter of presenilin 1 (PSEN1) significantly decreasing PSEN1 expression in vitro. For late-onset Alzheimer's disease (LOAD), numerous studies have reported inconsistent associations with a PSEN1 intronic polymorphism. We therefore hypothesized that linkage disequilibrium between the intronic PSEN1 polymorphism and the functional promoter polymorphism might explain the conflicting reports in LOAD. We analysed both variations in 356 LOAD patients and 230 controls in a population-based case-control study. In addition, we re-analysed all published literature on the PSEN1 intronic polymorphism in a meta-analysis. No significant association was found with the PSEN1 intronic or promoter polymorphism in our case-control sample. In the meta-analysis no major differences between patients and controls were found for the PSEN1 intronic variation. Together, our results do not support a major role for variable expression of PSEN1 in LOAD.

Linkage to chromosome 14q in Alzheimer's disease (AD) patients without psychotic symptoms

“…Sequencing of the gene in the most linked families did not detect any coding or splice site variations, yet a regulatory region that was not screened or a different gene in the region might be responsible for this signal. The possibility of a regulatory mutation has also been suggested, though inconsistently, by previous studies [Dermaut et al, 2001;Lambert et al, 2001;Araria-Goumidi et al, 2002].…”

Meta-analysis of genetic variability in the ?-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer?s disease

“…In this work, we report results from meta‐analyses carried out on the association between AD and genetic variants in genes involved in production (BACE1, CYP46, FE65) or degradation of Aβ: ACT Ala17Thr, BH I443V, lectin‐like OLR1 3′‐UTR (+1071), OLR1 3′‐UTR (+1073), and VLDLR 5′‐UTR (CGG‐repeat). In addition, we also display results from previously reported meta‐analyses on seven additional genes: cathepsin D (6), LBP‐1c/CP2/LSF (7), presenilin 1 (8), butyrylcholinesterase (9), PRNP (10), α2‐macroglobulin (11) and LRP1 (12).…”

Candidate Susceptibility Genes in Alzheimers Disease Are at High Risk for Being Forgotten - They Dont Give Peace of Mind...

“…These effects appeared to be independent of the ApoEε4 allele and no interaction with age or sex was detected. The relevance of this polymorphism, however, is also controversial [21,67,68].…”

“…TGF-β1, located on chromosome 19q13.1-13.3, is a cytokine reported to be overexpressed in AD brains [67]. TGF-β1 consists of three isoforms, derived from proteolytic processing of the 390-amino-acid precursor.…”