Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation - PubMed
4 hours ago
- #Alzheimer's Disease
- #Microglia
- #Neuroinflammation
- Alzheimer's Disease (AD) is traditionally characterized by Amyloid-β plaques and tau tangles, but these alone do not fully explain disease progression.
- Chronic neuroinflammation is identified as a key factor converting molecular pathology into synaptic failure and neurodegeneration.
- Aβ activates microglial and astrocytic immune responses through receptors like TREM2, TLRs, and RAGE, leading to inflammasome activation and cytokine release.
- Neuroinflammation re-engages developmental complement pathways (C1q-C3-CR3), causing excessive synaptic pruning linked to cognitive impairment.
- Reactive astrocytes impair glutamate and potassium homeostasis, promoting excitotoxic and metabolic stress.
- Inflammatory glia facilitate tau propagation via extracellular vesicles, and neurovascular inflammation disrupts blood-brain barrier integrity.
- Neuroinflammatory biomarkers (GFAP, sTREM2, YKL-40, etc.) provide dynamic insights into disease activity and treatment response.
- AD is positioned as a disorder of failed immune resolution, supporting immunomodulatory therapies aimed at restoring neuroimmune homeostasis.