ZNI Seminar Series: "Rare and Common Risk Variants for Late Onset Alzheimer’s Disease Implicate Myeloid Cell Function"

Wednesday, September 27 at 12:00pm to 1:00pm

Zilkha Neurogenetic Institute (ZNI), Herklotz Seminar Room (ZNI 112)
1501 San Pablo, Los Angeles, CA 90033

Late onset Alzheimer’s disease has a very strong genetic component which, in spite of many years’ study, is still poorly understood.  Genome-wide association studies of common variation have identified more than thirty loci influencing risk for disease. Pathway analysis has demonstrated that these loci are enriched for genes involved in biological functions that include lipid metabolism, endocytosis and immune response. Expression quantitative trait loci (eQTL) data and epigenetic annotation shows that the impact of AD risk variants is seen in myeloid lineage cells, and that AD heritability is enriched within the cistrome of the myeloid-specific transcription factor, PU.1.  Analysis of whole genome sequence data similarly implicates genes expressed in myeloid cells, including TREM2, ABCA7 and SORL1 as well as ABI3 and PLCG2.  Pathway analysis also links many of these genes to a network including PU.1.  Finally, experimentally altered PU.1 levels are correlated with phagocytic activity of mouse BV2 microglial cells, and specific changes in the expression of multiple myeloid-expressed genes.  Our results collectively suggest that lower SPI1 expression reduces AD risk by modulating myeloid cell gene expression and function.

Event Type

Lecture / Talk / Workshop

Campus

Health Sciences Campus

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