Do Microglia default on network maintenance in Alzheimer's disease?
Open accessAbstract
Although the cause of Alzheimer's disease (AD) remains unknown, a number of new findings suggest that the immune system may play a critical role in the early stages of the disease. Genome-wide association studies have identified a wide array of risk-associated genes for AD, many of which are associated with abnormal functioning of immune cells. Microglia are the brain's immune cells. They play an important role in maintaining the brain's extracellular environment, including clearance of aggregated proteins such as amyloid-β (Aβ). Recent studies suggest that microglia play a more active role in the brain than initially considered. Specifically, microglia provide trophic support to neurons and also regulate synapses. Microglial regulation of neuronal activity may have important consequences for AD. In this article we review the function of microglia in AD and examine the possible relationship between microglial dysfunction and network abnormalities, which occur very early in disease pathogenesis.
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The primary pathogenic process in AD is the accumulation of Aβ protein, which aggregates into extracellular amyloid plaques, the hallmark of this pathology.
“The primary pathogenic process in AD is the accumulation of Aβ protein. This protein aggregates into extracellular amyloid plaques, which are the hallmark of this pathology (Southam et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Southam et al., 2016
In healthy development of the brain, complement proteins participate in synapse pruning; synapses to be cleared express C3 and binding to CR3 on microglia results in microglial phagocytosis of the synapse.
“In the healthy development of the brain, the proteins of complement participate in synapse pruning. Synapses to be cleared express C3 and binding to CR3 on microglia, resulting in microglial phagocytosis of the synapse (Schafer et al., 2012; Southam et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Southam et al., 2016
In AD, mutations in ABCA7 can cause a loss of receptor activity, resulting in reduced microglia phagocytic function.
“In AD, mutations in ABCA7 can cause a loss of receptor activity, resulting in reduced microglia phagocytic function (Southam et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Southam et al., 2016
Altered microglial behavior could induce neuronal degeneration in AD.
“The altered microglial behavior could induce neuronal degeneration in AD (Southam et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Southam et al., 2016
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- Authors
- Southam, K. A., Vincent, A. J., & Small, D. H.
- Affiliations
- University of Tasmania (AU)
- Corresponding author
- Southam, Katherine A.
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2016-03-30
- Volume
- 51
- Issue
- 3
- Pages
- 657-669
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC4927862
- OpenAlex
- W2275287389
- Cited by
- 20
- References
- 155
- Citations by year
- 2024: 2 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 9
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion, cc-by-nc)
- Figshare (submittedVersion, cc-by-nc)
- Funders
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Humans, Synapses, Microglia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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