Analyst Luuk de Vries, PhD, is a contributing author on the publication "Human microglial transitions at the Aβ–tau inflection point associate with divergent pathways to dementia and resilience" published in Nature Medicine.
The study combines spatial transcriptomics and single-nucleus RNA sequencing of post-mortem human brain tissue to investigate why some individuals develop Alzheimer's disease while others remain cognitively resilient despite significant amyloid pathology. The authors identify a critical biological inflection point, the transition from amyloid-β-driven immune responses to tau-associated neurodegeneration, and show that microglial state transitions at this interface are key determinants of disease progression or resilience. Notably, cognitively intact octogenarians and centenarians were found to achieve resilience through distinct mechanisms, opening new avenues for therapeutic intervention.
Click here to access the article on Nature Medicine's website.