Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment

Kivisäkk, P; Carlyle, BC; Sweeney, T; Trombetta, BA; LaCasse, K; El-Mufti, L; Tuncali, I; Chibnik, LB; Das, S; Scherzer, CR; Johnson, KA; Dickerson, BC; Gomez-Isla, T; Blacker, D; Oakley, DH; Frosch, MP; Hyman, BT; Aghvanyan, A; Bathala, P; Campbell, C; Sigal, G; Stengelin, M; Arnold, SE

Journal article

Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment

Abstract:: BackgroundThe last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression of neurodegenerative dementias.MethodsWe evaluated a panel of four novel ultrasensitive electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins of interest in AD in plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)]. Two sets of banked plasma samples from the Massachusetts Alzheimer's Disease Research Center's longitudinal cohort study were examined: A longitudinal prognostic sample (n = 85) consisting of individuals with mild cognitive impairment (MCI) and 4 years of follow-up and a cross-sectional sample (n = 238) consisting of individuals with AD, other neurodegenerative diseases (OND), and normal cognition (CN).ResultsParticipants with MCI who progressed to dementia due to probable AD during follow-up had higher baseline plasma concentrations of pTau181, NfL, and GFAP compared to non-progressors. The best prognostic discrimination was observed with pTau181 (AUC = 0.83, 1.7-fold increase) and GFAP (AUC = 0.83, 1.6-fold increase). Participants with autopsy- and/or biomarker verified AD had higher plasma levels of pTau181, tTau and GFAP compared to CN and OND, while NfL was elevated in AD and further increased in OND. The best diagnostic discrimination was observed with pTau181 (AD vs CN: AUC = 0.90, 2-fold increase; AD vs. OND: AUC = 0.84, 1.5-fold increase) but tTau, NfL, and GFAP also showed good discrimination between AD and CN (AUC = 0.81–0.85; 1.5–2.2 fold increase).ConclusionsThese new ultrasensitive ECL plasma assays for pTau181, tTau, NfL, and GFAP demonstrated diagnostic utility for detection of AD. Moreover, the absolute baseline plasma levels of pTau181 and GFAP reflect cognitive decline over the next 4 years, providing prognostic information that may have utility in both clinical practice and clinical trial populations.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Kivisäkk, P., Carlyle, B. C., Sweeney, T., Trombetta, B. A., LaCasse, K., El-Mufti, L., Tuncali, I., Chibnik, L. B., Das, S., Scherzer, C. R., Johnson, K. A., Dickerson, B. C., Gomez-Isla, T., Blacker, D., Oakley, D. H., Frosch, M. P., Hyman, B. T., Aghvanyan, A., Bathala, P., … Arnold, S. E. (2023). Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment. Frontiers in Neurology, 14, 1069411–1069411.

MLA Style

Kivisäkk, P, et al. “Plasma Biomarkers for Diagnosis of Alzheimer's Disease and Prediction of Cognitive Decline in Individuals with Mild Cognitive Impairment.” Frontiers in Neurology, vol. 14, 2023, pp. 1069411–11.

Chicago Style

Kivisäkk, P, BC Carlyle, T Sweeney, et al. 2023. “Plasma Biomarkers for Diagnosis of Alzheimer's Disease and Prediction of Cognitive Decline in Individuals with Mild Cognitive Impairment.” Frontiers in Neurology 14: 1069411–11.
Print