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. 2017 Jul 12;12(7):e0177814.
doi: 10.1371/journal.pone.0177814. eCollection 2017.

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

Diego Mastroeni  1   2 , Shobana Sekar  3 , Jennifer Nolz  1 , Elaine Delvaux  1 , Katie Lunnon  4 , Jonathan Mill  4   5 , Winnie S Liang  3 , Paul D Coleman  1   2
Affiliations

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

Diego Mastroeni et al. PLoS One. .

Erratum in

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. ANK1 mRNA expression levels in hippocampal homogenates, AD CA1 pyramidal neurons AD CA1 astrocytes and AD CA1 microglia.
Bar graph depicts log2 fold change, comparing AD vs. age matched normal controls. No significant difference was detected in homogenates, AD neurons, or AD astrocytes. In stark contrast, a significant four-fold increase (p<0.001) was observed in AD microglia.
Fig 2
Fig 2. Significant, Log2 fold change(s) in genes containing ankyrin repeat domains in AD hippocampal homogenates, AD CA1 pyramidal neurons, AD CA1 astrocytes and AD CA1 microglia.
A) Significantly (p < .05) altered Ankyrin repeat containing genes in hippocampal homogenates in AD compared to ND. B) Significantly altered (p < .05) Ankyrin repeat containing genes in LCM neurons and glial cells (C). D) average log2 mRNA fold difference in ankyrin repeat genes in PD microglia from CA1 of the hippocampus compared to the same matched control subjects used in AD comparisons. LCM neurons, astrocytes and microglia were derived from the same human subjects. Detailed expression changes can be found in S1 Fig.
Fig 3
Fig 3. mRNA expression analysis of EWAS-related genes in AD CA1 pyramidal neurons AD CA1 astrocytes and AD CA1 microglia.
Only two of the seven identified transcripts in the EWAS study were significantly differentially expressed, BIN1 in AD neurons and SERPINF2 in AD microglia. * indicates p < .05.
See this image and copyright information in PMC

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