Alzheimer's Disease (AD) & Microglia

The proliferation and activation of microglia in the brain, particularly around amyloid plaques, is a significant characteristic of Alzheimer's disease (AD). Human genetic studies highlight the crucial role of microglia in the pathogenesis of AD. Notably, most risk genes associated with AD are highly, and often selectively, expressed by microglia in the brain (1).

There is increasing evidence suggesting that microglia play a protective role against the onset of AD. Impaired microglial functions and altered responses to beta-amyloid are linked to a heightened risk of developing AD. Conversely, substantial evidence also indicates that activated microglia can be detrimental to neurons. They can mediate synapse loss through the engulfment of synapses, likely via a complement-dependent mechanism. Additionally, microglia can exacerbate tau pathology and secrete inflammatory factors that may directly harm neurons or activate neurotoxic astrocytes (1).

Gene expression profiles reveal multiple states of microglial activation in neurodegenerative disease contexts. This variability might account for the differing roles of microglia in the development and progression of AD pathology (1)

Recent findings from gene network analyses highlight the enrichment of immune networks in Alzheimer's Disease (AD). Many genes within these networks are located in genomic regions that harbor both common and rare variants linked to an increased risk of developing AD. Among these genes, several are notably expressed by Microglia, the brain's resident immune cells. These include:

• cr1 gene


• ssp1 gene


• ms4as (membrane‑spanning 4‑domains subfamily A) genes


• trem2 gene


• abca7 gene


• cd33 gene


• inpp5d gene

These findings underscore the significant role of microglial gene expression in the context of AD risk (2).

References

(1) Hansen et al. 2018 J. Cell Biol. 217: 472
(2) Efthymiou & Goate 2017 Mol Neurodegener 12: 43

see also:
Alzheimer's disease (AD) & Brain-Gut-Microbiome-Axis / Gut-Brain Axis
Alzheimer's disease (AD) & Gut microbiota
Alzheimer's Disease (AD) & Pathogenicity / Pathology
CD33 (sialic acid binding Ig-like lectin 3) (Siglec-3)
Central Nervous System (CNS) & Neuroimmune Interactions
Cholesterol & Microglia
Microglia
Microglia & Neuroinflammation
Microgliosis / Gliosis