Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative
Open accessAbstract
Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer's disease (AD), the role of microglia is far to be elucidated. In this "mini-review" article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Aβ) plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Aβ production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V-VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown.
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Microglial activation plays a beneficial role in early stages of AD pathology but contributes to disease worsening in late stages of AD.
“several studies have suggested that microglial activation plays a beneficial role in early stages of AD pathology, but contributes to disease worsening in late stages of AD [66–68].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [67]
The section ‘Decoding Microglial Activation in Mouse Models and Human Brains’ says plaque-associated activation could be protective, though that role is under debate. For late-stage human AD, the paper instead describes attenuated activation and microglial degeneration (Figure 2; ‘Microglial Deterioration in the Hippocampus of AD Patients’). It does not support the claim that activation itself worsens disease in late stages. (LLM, conf=0.87)
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- Authors
- Navarro, V., Sanchez-Mejias, E., Jimenez, S., Muñoz-Castro, C., Sanchez-Varo, R., Davila, J. C., Vizuete, M., Gutierrez, A., & Vitorica, J.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-05-11
- Volume
- 10
- Pages
- 140-140
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5958192
- OpenAlex
- W2799331265
- Cited by
- 229
- References
- 53
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 33 · 2023: 35 · 2022: 32 · 2021: 31 · 2020: 43 · 2019: 27 · 2018: 3
- FWCI
- 11.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
- Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by)
- Funders
- Instituto de Salud Carlos III (PI15/00957 and PI15/00796)
- Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (CTS-2035)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, microglial activation, amyloid plaques, hippocampus, Braak stages, phosphorylated tau, dentate gyrus, neuroinflammation, regional heterogeneity
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