期刊
NEUROLOGY
卷 96, 期 5, 页码 E671-E683出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000011226
关键词
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资金
- Fondo de Investigaciones Sanitario/Instituto de Salud Carlos III [PI14/1561, PI17/01896]
- Alzheimer's Association [AARF-16-443577]
- Departament de Salut de la Generalitat de Catalunya [SLT002/16/00408]
- NIH [K23AG059888, K23AG061253, K08 AG052648, K24AG053435]
- Rio Hortega grant from Accion Estrategica en Salud [CM17/00074]
- Global Brain Health Institute
- Swedish Research Council [2018-05232, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- UK Dementia Research Institute at UCL
- Alzheimer Drug Discovery Foundation (ADDF), USA [RDAPB201809-2016615]
- Swedish Alzheimer Foundation [AF742881]
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish government [ALFGBG715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- Larry L. Hillblom Foundation [2018A-025-FEL]
- MRC [UKDRI-1003] Funding Source: UKRI
- Vinnova [2018-05232] Funding Source: Vinnova
Plasma NfL outperforms plasma t-tau in distinguishing between FTLD-S and AD-S, predicting clinical decline and survival, and correlating with regional cortical thickness; while plasma t-tau shows inferior performance in these aspects.
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.
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