ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity.

TitleANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity.
Publication TypeJournal Article
Year of Publication2017
AuthorsMastroeni D, Sekar S, Nolz J, Delvaux E, Lunnon K, Mill J, Liang WS, Coleman PD
JournalPLoS One
Volume12
Issue7
Paginatione0177814
Date Published2017
ISSN1932-6203
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Ankyrins, Case-Control Studies, Female, Hippocampus, Humans, Male, Microglia, Neurons, RNA, Messenger, Up-Regulation
Abstract

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.

DOI10.1371/journal.pone.0177814
Alternate JournalPLoS ONE
PubMed ID28700589
PubMed Central IDPMC5507536