Change in cerebrospinal fluid tau microtubule binding region detects symptom onset, cognitive decline, tangles, and atrophy in Dominantly Inherited Alzheimer's Disease.

Changes in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFT in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics. This article is protected by copyright. All rights reserved.