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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.
Glossary
- AD=
- Alzheimer disease;
- AD-S=
- Alzheimer disease syndromes;
- ALS-FTD=
- amyotrophic lateral sclerosis with frontotemporal dementia;
- AUC=
- area under the receiver operator characteristic curve;
- bvFTD=
- behavioral variant frontotemporal dementia;
- CBS=
- corticobasal syndrome;
- CDR+NACC/FTLD-SB=
- Clinical Dementia Rating plus National Alzheimer's Coordinating Center FTLD sum of boxes;
- FTLD=
- frontotemporal lobar degeneration;
- FTLD-S=
- frontotemporal lobar degeneration syndromes;
- HC=
- healthy control;
- MMSE=
- Mini-Mental State Examination;
- NfL=
- neurofilament light;
- nfvPPA=
- nonfluent/agrammatic variant of primary progressive aphasia;
- PSP=
- progressive supranuclear palsy;
- t-tau=
- total tau;
- svPPA=
- semantic variant of primary progressive aphasia;
- UCSF=
- University of California, San Francisco
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received March 5, 2020.
- Accepted in final form September 30, 2020.
- © 2020 American Academy of Neurology
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