Alzheimer’s disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes
Open accessAbstract
Alzheimer's disease (AD) is characterized by deficits in cerebral metabolic rates of glucose in the posterior cingulate (PC) and precuneus in AD subjects, and in APOEε4 carriers, decades before the onset of measureable cognitive deficits. However, the cellular and molecular basis of this phenotype remains to be clarified. Given the roles of astrocytes in energy storage and brain immunity, we sought to characterize the transcriptome of AD PC astrocytes. Cells were laser capture microdissected from AD (n = 10) and healthy elderly control (n = 10) subjects for RNA sequencing. We generated >5.22 billion reads and compared sequencing data between controls and AD patients. We identified differentially expressed mitochondria-related genes including TRMT61B, FASTKD2, and NDUFA4L2, and using pathway and weighted gene coexpression analyses, we identified differentially expressed immune response genes. A number of these genes, including CLU, C3, and CD74, have been implicated in beta amyloid generation or clearance. These data provide key insights into astrocyte-specific contributions to AD, and we present this data set as a publicly available resource.
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This analysis identified differential gene expression changes between normal aging and pathological astrocytes, providing a resource to distinguish between astrocytes in healthy aging and disease.
“This analysis identified differential gene expression changes between normal aging and pathological astrocytes, providing a resource to distinguish between astrocytes in healthy aging and disease (Berchtold et al., 2014; Sekar et al., 2015).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Sekar et al., 2015
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References 64 · Cited by 199
- Authors
- Sekar, S., McDonald, J., Cuyugan, L., Aldrich, J., Kurdoglu, A., Adkins, J., Serrano, G., Beach, T. G., Craig, D. W., Valla, J., Reiman, E. M., & Liang, W. S.
- Affiliations
- Translational Genomics Research Institute (US)
- Banner Sun Health Research Institute (US)
- Midwestern University (US)
- Corresponding author
- Liang, Winnie S.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 36
- Issue
- 2
- Pages
- 583-591
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4315763
- OpenAlex
- W2157585985
- Cited by
- 199
- References
- 64
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 26 · 2021: 25 · 2020: 23 · 2019: 21 · 2018: 21 · 2017: 14 · 2016: 15 · 2015: 10
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P30AG019610)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, astrocytes, transcriptome, mitochondrial genes, immune response genes, posterior cingulate cortex, precuneus, APOE ε4, brain glucose metabolism, amyloid-beta, clusterin, complement C3, CD74, NDUFA4L2, gene co-expression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Astrocytes, Brain, Complement C3, Electron Transport Complex IV, Energy Metabolism, Female, Humans, Immunity, Cellular, Male, Mitochondria, tRNA Methyltransferases, Gene Expression, Amyloid beta-Peptides, Protein Serine-Threonine Kinases, Sequence Analysis, RNA, Clusterin
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