Shifting paradigms: The central role of microglia in Alzheimer’s disease
Open accessAbstract
Recent human genetic studies have challenged long standing hypotheses about the chain of events in Alzheimer's disease (AD), as the identification of genetic risk factors in microglial genes supports a causative role for microglia in the disease. Parallel transcriptome and histology studies at the single-cell level revealed a rich palette of microglial states affected by disease status and genetic risk factors. Taken together, those findings support microglia dysfunction as a central mechanism in AD etiology and thus the therapeutic potential of modulating microglial activity for AD treatment. Here we review how human genetic studies discovered microglial AD risk genes, such as TREM2, CD33, MS4A and APOE, and how experimental studies are beginning to decipher the cellular functions of some of these genes. Our review also focuses on recent transcriptomic studies of human microglia from postmortem tissue to critically assess areas of similarity and dissimilarity between human and mouse models currently in use in order to better understand the biology of innate immunity in AD.
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Colocalization of reactive microglia with Aβ deposits is a hallmark of Alzheimer's disease pathology and has been reported in brains from AD mouse models.
“Colocalization of reactive microglia with Aβ deposits is a hallmark of AD pathology and has been reported also in brains from AD mouse models [102,103].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [103]
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References 137 · Cited by 84
Research works printed but not linked: 2
- Hirbec, H., Marmai, C., Duroux-Richard, I., Roubert, C., Esclangon, A., Croze, S., Lachuer, J., Peyroutou, R., Rassendren, F., 2018. The microglial reaction signature revealed by RNAseq from individual mice. Glia 66 (5), 971-986.
- Nugent, A.A., Lin, K., Van Lengerich, B., Lianoglou, S., Przybyla, L., Davis, S.S., Llapashtica, C., et al., 2019. TREM2 Regulates Microglial Cholesterol Metabolism Upon Chronic Phagocytic Challenge (August 29, 2019). NEURON-D-19-01269.SSRN: https://ssrn.com/abstract=3444596.
- Authors
- Schwabe, T., Srinivasan, K., & Rhinn, H.
- Affiliations
- Alector (United States) (US)
- Corresponding author
- Schwabe, Tina
- ORCID
- Srinivasan, Karpagam
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 143
- Pages
- 104962
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W3035380161
- Cited by
- 84
- References
- 137
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 20 · 2022: 18 · 2021: 13 · 2020: 4
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, microglia, microglial dysfunction, genetic risk factors, TREM2, CD33, apolipoprotein E, single-cell transcriptomics, postmortem brain, mouse model, innate immunity, microglial states, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Microglia, Genetic Predisposition to Disease
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