ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity.
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5507536?pdf=render |
| _version_ | 1811193007685238784 |
|---|---|
| author | Diego Mastroeni Shobana Sekar Jennifer Nolz Elaine Delvaux Katie Lunnon Jonathan Mill Winnie S Liang Paul D Coleman |
| author_facet | Diego Mastroeni Shobana Sekar Jennifer Nolz Elaine Delvaux Katie Lunnon Jonathan Mill Winnie S Liang Paul D Coleman |
| author_sort | Diego Mastroeni |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T00:01:12Z |
| format | Article |
| id | doaj.art-f4fbb189ce6a48aa8835a0d7476623c4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T00:01:12Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f4fbb189ce6a48aa8835a0d7476623c42022-12-22T03:56:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e017781410.1371/journal.pone.0177814ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity.Diego MastroeniShobana SekarJennifer NolzElaine DelvauxKatie LunnonJonathan MillWinnie S LiangPaul D ColemanRecent 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.http://europepmc.org/articles/PMC5507536?pdf=render |
| spellingShingle | Diego Mastroeni Shobana Sekar Jennifer Nolz Elaine Delvaux Katie Lunnon Jonathan Mill Winnie S Liang Paul D Coleman ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. PLoS ONE |
| title | ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. |
| title_full | ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. |
| title_fullStr | ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. |
| title_full_unstemmed | ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. |
| title_short | ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. |
| title_sort | ank1 is up regulated in laser captured microglia in alzheimer s brain the importance of addressing cellular heterogeneity |
| url | http://europepmc.org/articles/PMC5507536?pdf=render |
| work_keys_str_mv | AT diegomastroeni ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT shobanasekar ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT jennifernolz ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT elainedelvaux ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT katielunnon ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT jonathanmill ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT winniesliang ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity AT pauldcoleman ank1isupregulatedinlasercapturedmicrogliainalzheimersbraintheimportanceofaddressingcellularheterogeneity |