Microglia in Alzheimer's Disease: From Homeostatic Guardians to Multifaceted Drivers of Neuropathology.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic, molecular, and pre-clinical literature.
PubMed 42505400 · doi:10.3390/cells15141291
What was done
This narrative review synthesized literature published between 2020 and 2026 on microglial biology in Alzheimer's disease. The authors focused on disease-associated microglial ontogeny, metabolic reprogramming, immune checkpoints, and glial-immune crosstalk.
What was found
The abstract reports qualitative mechanistic pathways without quantitative numerical metrics or effect sizes. It describes a microglial phenotype shift from early protective phagocytic states (M2, DAM1/2) to late pro-inflammatory and exhausted states (M1, terminal inflammatory microglia, lipid droplet-accumulating microglia). Key implicated pathways include TREM2/SYK, Piezo1, TAM receptors, and metabolic regulators (HK2, iron, APOE4-driven lipid metabolism), alongside intercellular communication via IL-3, complement C3, MHC-I, and MHC-II.
Why it matters
It provides an updated framework of microglial heterogeneity in Alzheimer's disease, emphasizing stage-specific targeting of functional phenotypes over broad immunosuppression.
Limits
This is a narrative review with no systematic search protocol, formal risk-of-bias assessment, or reported study count. The described mechanisms rely heavily on pre-clinical models, and no quantitative clinical trial data are evaluated.
Cited by
- supports Microglial phagocytosis of proteins is impaired in individuals with Alzheimer's disease.
- context Elevated blood sugar and systemic inflammation polarize microglia to an M1 phenotype that cannot phagocytize.