INTRODUCTION: Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints. METHODS: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (n=598) and/or cerebrospinal fluid (CSF; n=154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants (n=598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive; 29% overweight/obese; and 64% with mild-to-moderate kidney disease. Gaussian-mixture models, logistic regression, and receiver operating curve analyses were performed. RESULTS: Plasma p-tau217 was associated with elevated Aβ deposition and accurately classified Aβ-positive participants (PET: AUC: 94%-97%, cutpoint≥.338 pg/mL; CSF: AUC = .84, cutpoint≥.307 pg/mL). DISCUSSION: Plasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort, and superior to other plasma biomarkers assessed. Longitudinal analyses assessing impact of comorbidities on p-tau217 utility for disease progression are underway.

Drs. Rudolph, Sutphen, Register, Rundle, Hughes, Solingapuram Sai, and Whitlow, have no conflicts of interest to disclose. Drs. Bateman and Lockhart receive funding from the Alzheimer's Association. Dr. Bateman has also received honoraria from Efficient CME, PeerView CME, and Novo Nordisck in the last two years. Dr. Craft reports disclosures for vTv Therapeutics, T3D Therapeutics, Cyclerion Inc., and Cognito Inc. Dr. Mielke consults for or serves on advisory boards for Biogen, Eisai, Lilly, Merck, Roche, and Siemens Healthineers.

This work was supported by the Wake Forest University School of Medicine's Alzheimer's Disease Research Center (P30AG049638, P30AG072947, R01AG054069, R01AG058969, and T32AG033534), which is funded by the National Institute on Aging (NIA). Additional support was provided by the Department of Gerontology and Geriatric Medicine and Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine. Plasma biomarker analyses were completed in part by the NCRAD Biomarker Assay Laboratory as part of the Alzheimer's Disease Center Fluid Biomarker (ADCFB) Initiative, which receives government support under a cooperative agreement grant (U24 AG021886) awarded by the National Institute on Aging (NIA). Plasma p-tau217 analytes were processed at Neurocode (Bellingham, WA) and funded by ALZpath (Carlsbad CA). This study would not have been possible without the commitment and support of our valued WFADRC staff and study participants. This study was supported by the following funding sources: Rudolph reports funding for this work from National Institutes of Health (NIH) P30AG072947 and T32AG033534. Sutphen reports funding for this work from NIH P30AG049638 and P30AG072947 and additional funding from other NIH grants to the institution including T32AG033534. Register reports funding for this work from NIH P30AG049638 and P30AG072947 and additional funding from other NIH grants to the institution. Lockhart reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants to the institution. Rundle reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants to the institution. Hughes reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants to the institution. Bateman reports funding for this work from NIH P30AG072947, other NIH grants, and funding from ASPECT 20-AVP-786-306 to the institution. Solingapuram Sai reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants to the institution. Whitlow reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants to the institution. Craft reports funding for this work from NIH P30AG072947 and additional funding from other NIH grants. Mielke reports funding for this work from NIH P30AG072947 and U24 AG082930.

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