In mice, disease-associated microglia proliferate so much that they become senescent. Plaques then run amok and synapses are lost.
The anti-tau immunotherapy did not slow cognitive decline among people in the earliest stages of AD, nor did it evoke changes on tau-PET scans.
In the face of aging or amyloidosis, microglia lacking C9ORF72 ramped up interferon genes, accumulated lysosomes, and ate synapses.
The tau vaccine evoked a robust anti-tau antibody response, which curbed the rise in plasma NfL and CSF p-tau over two years. Cognitive decline continued.