Evaluation of Plasma P-tau217 for Detecting Amyloid Pathology in a Diverse and Heterogeneous Community-based Cohort

Overview

Journal medRxiv

Date 2025 Feb 20

PMID 39974029

Authors

Marc D Rudolph

Courtney L Sutphen

Thomas C Register

Samuel N Lockhart

Melissa M Rundle

Timothy M Hughes

James R Bateman

Kiran K Solingapuram Sai

Christopher T Whitlow

Suzanne Craft

Michelle M Mielke

Affiliations

Soon will be listed here.

Abstract

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 (=598) and/or cerebrospinal fluid (CSF; =154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants (=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.

References

Rudolph M, Sutphen C, Register T, Whitlow C, Solingapuram Sai K, Hughes T . Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort. Alzheimers Dement. 2024; 20(6):4159-4173. PMC: 11180870. DOI: 10.1002/alz.13835. View

Hansson O, Blennow K, Zetterberg H, Dage J . Blood biomarkers for Alzheimer's disease in clinical practice and trials. Nat Aging. 2023; 3(5):506-519. PMC: 10979350. DOI: 10.1038/s43587-023-00403-3. View

Albert M, DeKosky S, Dickson D, Dubois B, Feldman H, Fox N . The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):270-9. PMC: 3312027. DOI: 10.1016/j.jalz.2011.03.008. View

La Joie R, Ayakta N, Seeley W, Borys E, Boxer A, DeCarli C . Multisite study of the relationships between antemortem [C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement. 2018; 15(2):205-216. PMC: 6368897. DOI: 10.1016/j.jalz.2018.09.001. View

Hughes T, Lockhart S, Suerken C, Jung Y, Whitlow C, Bateman J . Hypertensive Aspects of Cardiometabolic Disorders Are Associated with Lower Brain Microstructure, Perfusion, and Cognition. J Alzheimers Dis. 2022; 90(4):1589-1599. PMC: 9764872. DOI: 10.3233/JAD-220646. View

Thijssen E, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L . Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration. Nat Med. 2020; 26(3):387-397. PMC: 7101073. DOI: 10.1038/s41591-020-0762-2. View

Schindler S, Petersen K, Saef B, Tosun D, Shaw L, Zetterberg H . Head-to-head comparison of leading blood tests for Alzheimer's disease pathology. Alzheimers Dement. 2024; 20(11):8074-8096. PMC: 11567821. DOI: 10.1002/alz.14315. View

Farrell M, Jiang S, Schultz A, Properzi M, Price J, Becker J . Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation. Neurology. 2020; 96(4):e619-e631. PMC: 7905788. DOI: 10.1212/WNL.0000000000011214. View

Knopman D, Lundt E, Therneau T, Albertson S, Gunter J, Senjem M . Association of Initial β-Amyloid Levels With Subsequent Flortaucipir Positron Emission Tomography Changes in Persons Without Cognitive Impairment. JAMA Neurol. 2020; 78(2):217-228. PMC: 7573795. DOI: 10.1001/jamaneurol.2020.3921. View

10.

Buckley C, Sherwin P, Smith A, Wolber J, Weick S, Brooks D . Validation of an electronic image reader training programme for interpretation of [18F]flutemetamol β-amyloid PET brain images. Nucl Med Commun. 2016; 38(3):234-241. PMC: 5318150. DOI: 10.1097/MNM.0000000000000633. View

11.

Syrjanen J, Campbell M, Algeciras-Schimnich A, Vemuri P, Graff-Radford J, Machulda M . Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities. Alzheimers Dement. 2021; 18(6):1128-1140. PMC: 8957642. DOI: 10.1002/alz.12466. View

12.

Rowe C, Pejoska S, Mulligan R, Jones G, Chan J, Svensson S . Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. J Nucl Med. 2013; 54(6):880-6. DOI: 10.2967/jnumed.112.114785. View

13.

Mattsson-Carlgren N, Collij L, Stomrud E, Binette A, Ossenkoppele R, Smith R . Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies. JAMA Neurol. 2023; 81(1):69-78. PMC: 10696515. DOI: 10.1001/jamaneurol.2023.4596. View

14.

Amft M, Ortner M, Eichenlaub U, Goldhardt O, Diehl-Schmid J, Hedderich D . The cerebrospinal fluid biomarker ratio Aβ42/40 identifies amyloid positron emission tomography positivity better than Aβ42 alone in a heterogeneous memory clinic cohort. Alzheimers Res Ther. 2022; 14(1):60. PMC: 9044878. DOI: 10.1186/s13195-022-01003-w. View

15.

Stevens L, Levey A . Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol. 2009; 20(11):2305-13. DOI: 10.1681/ASN.2009020171. View

16.

Collij L, Salvado G, Shekari M, Lopes Alves I, Reimand J, Wink A . Visual assessment of [F]flutemetamol PET images can detect early amyloid pathology and grade its extent. Eur J Nucl Med Mol Imaging. 2021; 48(7):2169-2182. PMC: 8175297. DOI: 10.1007/s00259-020-05174-2. View

17.

Binette A, Janelidze S, Cullen N, Dage J, Bateman R, Zetterberg H . Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance. Alzheimers Dement. 2022; 19(4):1403-1414. PMC: 10499000. DOI: 10.1002/alz.12787. View

18.

Villeneuve S, Rabinovici G, Cohn-Sheehy B, Madison C, Ayakta N, Ghosh P . Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. Brain. 2015; 138(Pt 7):2020-33. PMC: 4806716. DOI: 10.1093/brain/awv112. View

19.

Mielke M, Dage J, Frank R, Algeciras-Schimnich A, Knopman D, Lowe V . Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med. 2022; 28(7):1398-1405. PMC: 9329262. DOI: 10.1038/s41591-022-01822-2. View

20.

OBryant S, Petersen M, Hall J, Johnson L . Medical comorbidities and ethnicity impact plasma Alzheimer's disease biomarkers: Important considerations for clinical trials and practice. Alzheimers Dement. 2022; 19(1):36-43. DOI: 10.1002/alz.12647. View