Human microglial transitions at the Aβ–tau inflection point associate with divergent pathways to dementia and resilience

To investigate the role of microglial transitions at the Aβ–tau intersection in determining pathways leading to dementia and cognitive resilience.

Microglial modulation at the Aβ–tau interface is a determinant of cognitive resilience.
Octogenarians without dementia exhibited early PIG responses despite Aβ burden.
Cognitively intact centenarians showed late PIG activation and resisted downstream tau accumulation.

The study's cohorts were selected to minimize confounding factors, which may limit generalizability.
Age-related variability and co-pathologies in the datasets could confound results.

Nature Medicine

by Ashley Lu, Wei-Ting Chen, Maria Dalby, Diego Sainz Garcia, Marisa Vanheusden, Luuk E. de Vries, Veerle van Lieshout, Araks Martirosyan, Katleen Craessaerts, Sebastiaan Moonen, Magdalena Zielonka, Iordana Chrysidou, Anke Misbaer, Leen Wolfs, Benjamin Pavie, Dick Swaab, Dietmar Rudolf Thal, Inge Huitinga, Annemieke Rozemuller, Susan Karijn Rohde, Marc Hulsman, Henne Holstege, Rita Balice-Gordon, Niels Plath, Mark Fiers, Bart De Strooper
June 4, 2026