In asymptomatic carriers of autosomal dominant Alzheimer’s disease, tau pathology is not significantly different from that in healthy controls overall, but is detectable in a subset of individuals with a shorter estimated time to symptom onset, indicating that tau accumulation occurs late in the preclinical phase.

A genetic mutation causes excess amyloid-beta to build up in the brain, especially in the striatum. This triggers tau proteins to misfold and spread from the memory centers to other brain regions. When tau reaches key network areas, it disrupts how brain cells communicate, causing a temporary increase in activity as the brain tries to compensate. This compensation fails as tau spreads further, and only when tau accumulates enough in these regions does it become detectable — right before symptoms appear.