TY - JOUR
T1 - ANK1 is up-regulated in laser captured microglia in Alzheimer’s brain; the importance of addressing cellular heterogeneity
AU - Mastroeni, Diego
AU - Sekar, Shobana
AU - Nolz, Jennifer
AU - Delvaux, Elaine
AU - Lunnon, Katie
AU - Mill, Jonathan
AU - Liang, Winnie S.
AU - Coleman, Paul
N1 - Funding Information:
The authors declare no competing financial or conflict of interests. We are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human brain samples. This work was supported by New Investigator Research Grant-Alzheimer’s Association NIRG-15-321390 and Arizona Department of Health ADHS16-104646 FY2015-16 to D.M.
PY - 2017/7
Y1 - 2017/7
N2 - 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 we isolated microglial, astrocytes and neurons 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, we show 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.
AB - 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 we isolated microglial, astrocytes and neurons 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, we show 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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U2 - 10.1371/journal.pone.0177814
DO - 10.1371/journal.pone.0177814
M3 - Article
C2 - 28700589
AN - SCOPUS:85023160642
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 7
M1 - e0177814
ER -