Longevity & AgingHow Immune System Dysfunction Drives Alzheimer's Disease Progression
A comprehensive 2026 review in Nature Reviews Neuroscience synthesizes evidence that peripheral immune dysfunction is not merely a consequence of Alzheimer's disease (AD) but a driving force. GWAS data link numerous AD risk genes to immune cells. Microglia adopt distinct disease states (MGnD, DAM, TIM) that can either clear or worsen amyloid and tau pathology. T cells, B cells, monocytes, and neutrophils each modulate neuroinflammation, plaque clearance, and neurodegeneration. Immunosenescence, epigenetic reprogramming, and lipid metabolic dysfunction in aging immune cells amplify risk. The authors argue that immune checkpoint inhibition, cytokine targeting, and personalized immune profiling represent promising next-generation therapeutic strategies for AD.
