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P1‐283: Mitochondrial DNA haplogroup, AD incidence, and cognitive function: The Cache County study on memory, health, and aging
Author(s) -
Kauwe John,
Cawthon Richard,
Kerber Richard,
Tschanz JoAnn,
Ward David,
Norton Maria,
Zandi Peter,
WelshBohmer Kathleen,
Breitner John,
Munger Ronald
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.564
Subject(s) - haplogroup , human mitochondrial dna haplogroup , demography , incidence (geometry) , population , mitochondrial dna , dementia , haplotype , genotype , medicine , gerontology , genetics , biology , disease , gene , physics , sociology , optics
Background: Sortilin-related receptor 1 (SORL1) plays a key role in the recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways. In fact, the APP holoprotein is synthesized in the endoplasmic reticulum and Golgi; then, it is processed by alphaor betasecretase and, successively, by thegamma-secretase complex generatingA-beta fragments.Alternatively, SORL1 binds APP holoprotein acting as a sorting receptor. Absence of SORL1 switches APP away from the retromer recycling pathway directing it into the beta-secretase pathway and so increasingA-beta peptide production.Recently, Rogaeva described an association between some SORL1 genetic variants and late-onset Alzheimer’s disease (AD). Methods: After obtaining informed consent, blood samples were taken from patients and control subjects. Genomic DNAwas extracted from peripheral blood leukocytes. Genetic analysis was performed using Direct sequencing by DNA sequencer Beckman CEQ 8000 and HRM analysis by RotorGene 6000 real-time analyzer. Results: The aim of this study was to study allelic variants of SORL1 to verify if they could be genetics markers of AD and/or predictors of MCI to AD conversion. We carried out a genetic analysis on SORL1 gene using tagging SNPs representative of three different LD blocks: rs641120, rs1010159 and rs641120. We found that rs641120 and rs1010159 frequencies of SORL1 were increased in the cases compared to controls. Moreover, rs641120 SNP seems to be more associated to the MCI subjects converted in AD respect to no-converted MCI group. Conclusions:Our results support the evidence that genetic variants of SORL1 affect the susceptibility to develop AD; moreover, this gene could be considered a genetic determinant to predict the progression of clinical phenotype from MCI to Alzheimer’s disease.