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Recent epigenetic association studies have identified a new gene, ANK1, in the pathogenesis of Alzheimer’s disease (AD). Although strong associations were observed, brain homogenates were used to generate the data, introducing complications because of the range of cell types analyzed. In order to address the issue of cellular heterogeneity in homogenate samples microglial, astrocytes and neurons were isolated by laser capture microdissection from CA1 of hippocampus in the same individuals with a clinical and pathological diagnosis of AD and matched control cases. Using this unique RNAseq data set, this study shows that in the hippocampus, ANK1 is significantly (p<0.0001) up-regulated 4-fold in AD microglia, but not in neurons or astrocytes from the same individuals. These data provide evidence that microglia are the source of ANK1 differential expression previously identified in homogenate samples in AD.
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Number of cases: 12
Alzheimer's disease (AD): 6
Parkinson's disease (PD): 6
Number of controls: 6
This work was supported by New Investigator Research Grant-Alzheimer’s Association NIRG-15-321390 and Arizona Department of Health ADHS16-104646 FY2015-16.