Overview
- - A JAMA Network Open analysis of 2,766 cognitively healthy women in WHIMS found baseline plasma p-tau217 strongly predicted incident cognitive outcomes over up to 25 years (per 1 SD: HR 2.43 for MCI/dementia, 1.94 for MCI, 3.17 for dementia).
- - Predictive strength varied by subgroup, with stronger associations in women older than 70, APOE ε4 carriers, and for some outcomes in White vs Black women, and a greater dementia link among those randomized to estrogen plus progestin therapy.
- - Discriminative performance improved when combining p-tau217 with age (AUC 72.7% for dementia), though authors caution the assay is not ready for general population screening.
- - Separately, a Nature Aging study from Scripps Research used structural proteomics to detect conformational changes in three plasma proteins (C1QA, clusterin, ApoB) that classified cognitively normal, MCI, and Alzheimer’s cases with about 83% accuracy and tracked progression at ~86%.
- - The structure-based markers correlated with cognitive scores and showed moderate MRI associations, and both research lines call for larger, more diverse validation and standardization before clinical screening use.