Abstract
The first and most firmly established genetic risk factor for sporadic late onset Alzheimer’s disease (LOAD) is the e4 allele of the apolipoprotein E (APOE) gene [1]. Carrying the APOEe4 variant significantly increases the lifetime risk for LOAD, with the number of copies present indicative of level of risk [1,2] and is associated with lower age of clinical disease onset [1,3–6]. Furthermore, genome-wide association studies (GWAS) for sporadic LOAD confirmed that APOE is the major susceptibility genomic region for the disease and reported significant associations with markers within the APOE linkage disequilibrium (LD) locus (contains APOE, TOMM40 and APOC1 genes). The strongest association signal (by wide margin) in these studies was found at the APOE LD region and no other LOAD-association in the human genome remotely approached the same level of significance [7–10]. However, the molecular mechanism underlying the reported genetic LOAD-associations with APOE LD region in general and APOEe4 haplotype in particular has yet to be discovered.
Highlights
The first and most firmly established genetic risk factor for sporadic late onset Alzheimer’s disease (LOAD) is the e4 allele of the apolipoprotein E (APOE) gene [1]
A recent study showed that endoplasmic reticulum (ER)-mitochondrial communication and mitochondria associated ER membranes (MAM) function-as measured by the synthesis of phospholipids and of cholesteryl esters, respectively-are increased significantly in cells treated with APOEe4-containing astrocyte-conditioned media (ACM) as compared to those treated with APOEe3-containing ACM [16]
We showed that SNP rs429358, that defines the APOEe4 haplotype, has a significant effect on APOE-mRNAs levels in temporal cortex obtain from LOAD cases
Summary
The first and most firmly established genetic risk factor for sporadic late onset Alzheimer’s disease (LOAD) is the e4 allele of the apolipoprotein E (APOE) gene [1]. William K Gottschalk1, Mirta Mihovilovic1, Allen D Roses1,3, and Ornit Chiba-Falek1,2,* 1Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA Carrying the APOEe4 variant significantly increases the lifetime risk for LOAD, with the number of copies present indicative of level of risk [1,2] and is associated with lower age of clinical disease onset [1,3,4,5,6].
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