Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease. (2nd February 2021)

• Record Type: Journal Article
• Authors: Illán-Gala, Ignacio; Lleo, Alberto; Karydas, Anna; Staffaroni, Adam M.; Zetterberg, Henrik; Sivasankaran, Rajeev; Grinberg, Lea T.; Spina, Salvatore; Kramer, Joel H.; Ramos, Eliana M.; Coppola, Giovanni; La Joie, Renaud; Rabinovici, Gil D.; Perry, David C.; Gorno-Tempini, Maria Luisa; Seeley, William W.; Miller, Bruce L.; Rosen, Howard J.; Blennow, Kaj; Boxer, Adam L.; Rojas, Julio C.
• Is Part Of: Neurology. Volume 96:Number 5(2021)
• Page Start: e671
• Page End: e683
• Publication Date: 2021-02-02
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000011226
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically diagnosed Alzheimer disease syndromes (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses. Methods: We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression, and survival, and cortical thickness. Results: Plasma NfL, but not plasma t-tau, discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology-confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone. Conclusion: Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S. Classification of Evidence: This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance vs plasma t-tau in FTLD and AD.