Plasma p-tau181 and p-tau217 in discriminating PART, AD and other key neuropathologies in older adults

• DOI: 10.1007/s00401-023-02570-4
• Publication Date: 2023-04-09T11:02:31Z
• Authors: Lei Yu; Patricia A. Boyle; Shorena Janelidze; Vladislav A. Petyuk; Tianhao Wang; David A. Bennett; Oskar Hansson; Julie A. Schneider
• Keywords: Original Paper; Cerebral Amyloid Angiopathy; Aging; Amyloid beta-Peptides; Alzheimer Disease; Humans; Brain; tau Proteins; Biomarkers; 3. Good health; Aged

We examined whether plasma p-tau181 and p-tau217 are specific biomarkers of pathologically confirmed Alzheimer's disease (AD). In particular, we investigated the utility p-tau for differentiating AD from primary age-related tauopathy (PART), as well with mixed pathologies. Data came 269 older adults who participated in Religious Orders Study or Rush Memory Aging Project. Blood samples were collected during annual clinical evaluations. Participants died underwent brain autopsy. P-tau181 quantified proximate to death (average interval before death: 1.4 years) using Lilly-developed MSD immunoassays. Uniform neuropathologic evaluations assessed AD, PART, other common degenerative cerebrovascular conditions. Plasma was more strongly correlated β-amyloid paired helical filament tau (PHFtau) tangles than p-tau181. Both markers associated greater odds but had higher accuracy (area under ROC curve (AUC): 0.83) (AUC: 0.76). almost exclusively pathologic indices exception cerebral amyloid angiopathy. Compared p-tau181, showed a AUC (0.82 versus 0.74) PART. For either p-tau, did not observe level difference between individuals alone those summary, p-tau181and specifically pathological changes. Further, our data provide initial evidence that may be able differentiate PART comparable burdens tangle pathology. These results demonstrate specificity supporting its use identify patients suitable anti-AD therapies including immunotherapies.