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. 2025 May;21(5):e70288.
doi: 10.1002/alz.70288.

The performance of plasma p-tau217 in Black middle-aged and older adults

Gilda E Ennis  1   2 , Derek Norton  1   2   3 , Rebecca E Langhough  1   2   4 , Diane C Gooding  1   2   5 , Fabu P Carter  1   2 , Rachael Wilson  1   4 , Megan Zuelsdorff  1   4   6 , Shenikqua Bouges  1   2   7 , Sanjay Asthana  1   2 , Sterling C Johnson  1   2   4 , Henrik Zetterberg  1   8   9   10   11   12 , Carey E Gleason  1   2   7
Affiliations

The performance of plasma p-tau217 in Black middle-aged and older adults

Gilda E Ennis et al. Alzheimers Dement. 2025 May.

Abstract

Introduction: Medical conditions prevalent in Black adults within the United States have been associated with plasma tau phosphorylated at threonine 217 (p-tau217); however, insufficient p-tau217 research has been conducted with Black adults.

Methods: Participants included n = 233 predominantly cognitively unimpaired adults enrolled in the African Americans Fighting Alzheimer's in Midlife study. Subsamples had creatinine (n = 137) and positron emission tomography (PET; amyloid-PET = 65 [amyloid-PET-positive = 16/65]; tau-PET = 70). We tested whether p-tau217 (ALZPath, Inc.) varied by medical condition and amyloid- and tau-PET-positivity status and assessed the diagnostic accuracy of p-tau217.

Results: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, cardiovascular disease (CVD), and amyloid- and tau-PET-positive status demonstrated higher p-tau217. Effect sizes (rpb): eGFR <60 group = 0.48, CVD = 0.25, amyloid-PET-positive status = 0.54; tau-PET-positive status = 0.56. Lower eGFR was related to higher p-tau217 when adjusting for amyloid-PET. For abnormal amyloid-PET and tau-PET, p-tau217 exhibited areas under the curve of 0.90 and 0.89, respectively.

Discussion: Plasma p-tau217 showed promise as an Alzheimer's biomarker in Black adults; however, kidney function and CVD should be considered when interpreting levels.

Highlights: Plasma tau phosphorylated at threonine 217 (p-tau217) was tested in a sample of Black middle-aged and older adults. Level of p-tau217 was higher in impaired kidney function and cardiovascular disease. Obesity and diabetes were not related to p-tau217. Level of p-tau217 was higher in amyloid- and tau-PET-positive status. Plasma p-tau217 showed good receiver-operating characteristic area under the curve for abnormal amyloid- and tau-PET.

Keywords: African American; Alzheimer's disease; amyloid PET positivity; cardiovascular disease; estimated glomerular filtration rate; kidney function; medical comorbidities; plasma p‐tau217; tau‐PET positivity.

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Conflict of interest statement

Carey E. Gleason is a scientific advisor for Huntington Research Institute, is a member of Alzheimer's Disease Research Center External Advisory Boards (Stanford University; University of New Mexico), is the Chair of the Institutional Data and Safety Monitoring Board for a National Institute on Aging (NIA)–funded study (R01‐AG074971), and has been a scientific advisor for a documentary film Matter of Mind: My Alzheimer's produced in partnership with the Public Broadcasting Service. Carey E. Gleason and Megan Zuelsdroff are members of the Scientific Advisory Board for an NIA‐funded study (UH2AG083258). Megan Zuelsdroff is a Senior Associate Editor for Alzheimer's & Dementia. Sanjay Asthana was an editor of Hazzard's Geriatric Medicine and Gerontology (McGraw Hill). Sterling C. Johnson has served as a consultant to Enigma and ALZpath. Henrik Zetterberg. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Gilda E. Ennis, Derek Norton, Rebecca E. Langhough, Diane C. Gooding, Fabu P. Carter, Rachael Wilson, and Shenikqua Bouges have nothing to disclose. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Scatterplots illustrating associations of estimated glomerular filtration rate, body mass index, systolic blood pressure, and age with plasma p‐tau217. 1Association was not significant when adjusting for age and sex.
FIGURE 2
FIGURE 2
Box plots illustrate unadjusted associations between categorical measures of medical conditions and plasma p‐tau217. 1 P‐values for post hoc tests performed following a significant (p < 0.05) omnibus test. 2Associations were not significant when adjusting for age and self‐identified sex. BMI, body mass index; HTN, hypertension.
FIGURE 3
FIGURE 3
Box plots illustrate unadjusted associations between amyloid‐ and tau‐PET positivity and plasma p‐tau217. Scatter labeled according to kidney function categories. Dashed lines in (A) and (B) represent the p‐tau217 cut‐point for each AD biomarker. Beneath each box plot is a cross‐tabulation table showing the count within each kidney function and PET‐positivity status category. A, amyloid; PET, positron emission tomography; T, tau.
FIGURE 4
FIGURE 4
ROC curves for plasma p‐tau217 in detecting amyloid‐ and tau‐PET positivity. Plasma p‐tau217 cut‐points were 94% sensitive and 80% specific for amyloid‐PET‐positive status and 75% sensitive and 93% specific for tau‐PET‐positive status. Beneath each ROC curve is a cross‐tabulation table depicting the count in each plasma p‐tau217 and PET biomarker positivity status category. DVR, distribution volume ratio; PET, positron emission tomography; PiB, Pittsburgh Compound B; ROC, Receiver‐operating characteristic; ROI, region of interest; SUVR, standardized uptake value ratio.
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