ANK1 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 ColemanPublished in: PloS one (2017)
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.
Keyphrases
- inflammatory response
- neuropathic pain
- single cell
- electronic health record
- spinal cord
- big data
- cerebral ischemia
- white matter
- transcription factor
- cognitive decline
- resting state
- dna methylation
- gene expression
- copy number
- machine learning
- multiple sclerosis
- genome wide
- stem cells
- cell therapy
- lps induced
- spinal cord injury
- high resolution
- high speed
- mass spectrometry
- subarachnoid hemorrhage
- protein kinase