Publications by authors named "Andrew C Graham"
Article Synopsis
- The APOE-ε4 allele is linked to an increased risk of Alzheimer's disease (AD) due to its role in amyloid deposition, but there's ongoing debate about whether it accounts for all genetic variation in the APOE gene region.
- A genome-wide association study involving over 5,000 APOE-ε4 homozygous individuals discovered a significant association between a novel genetic locus (DAB1) and AD, but no strong connections were found within the APOE locus itself.
- Further analysis of the DAB1-RELN pathway revealed that this pathway is also associated with AD, implying a potential interaction between the APOE gene and the DAB1-RELN pathway that might influence the development of AD.
Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease.
View Article and Find Full Text PDFGenome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer's disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decrease Trem2 expression, and in parallel from knock-in mice heterozygous or homozygous for the Trem2 R47H AD risk variant. The prevailing phenotype of Trem2 R47H knock-in mice was decreased expression levels of Trem2 in microglia, which resulted in decreased density of microglia in the hippocampus.
View Article and Find Full Text PDF