You are here

Methionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts.

TitleMethionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts.
Publication TypeJournal Article
Year of Publication2019
AuthorsConner SC, Benayoun L, Himali JJ, Adams SL, Yang Q, DeCarli C, Blusztajn JK, Beiser A, Seshadri S, Delalle I
JournalJ Alzheimers Dis
Volume68
Issue1
Pagination357-365
Date Published2019
ISSN1875-8908
Abstract

Genome-wide association studies identified a single nucleotide polymorphism (SNP) in the MSRB3 gene encoding Methionine Sulfoxide Reductase-B3 (MsrB3) to be associated with the risk for low hippocampal volume and late onset Alzheimer's disease (AD). Subsequently, we identified AD-associated abnormal patterns of neuronal and vascular MsrB3 expression in postmortem hippocampi. The present study investigated the relationship between the MSRB3 SNP rs61921502, G (minor/risk allele) and MRI measures of brain injury including total brain volume, hippocampal volume, and white matter hyperintensities using linear regression models; the presence of brain infarcts using logistic regression models; and the incidence of stroke, dementia, and AD using Cox proportional hazards models in 2,038 Framingham Heart Study Offspring participants with MRI administered close to examination cycle 7 (1998-2001). Participants with neurological conditions that impede evaluation of vascular pathology by MRI, i.e., brain tumors, multiple sclerosis, and major head trauma, were excluded from the study. When adjusted for age and age squared at MRI exam, sex, and presence of Apolipoproteinɛ4 allele (APOE4), individuals with MSRB3 rs61921502 minor allele had increased odds for brain infarcts on MRI compared to those with no minor allele. However, in stratified analyses, MSRB3 rs61921502 minor allele was significantly associated with increased odds for MRI brain infarcts only in the absence of APOE4.

DOI10.3233/JAD-180977
Pubmed Linkhttps://www.ncbi.nlm.nih.gov/pubmed/30775993?dopt=Abstract
page_expoExternal
Alternate JournalJ. Alzheimers Dis.
PubMed ID30775993
PubMed Central IDPMC6481535
Grant ListRF1 AG057768 / AG / NIA NIH HHS / United States
UH3 NS100605 / NS / NINDS NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
T32 GM074905 / GM / NIGMS NIH HHS / United States
R01 AG042292 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
R56 AG057768 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
R01 AG057768 / AG / NIA NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
R01 AG045031 / AG / NIA NIH HHS / United States

Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer