Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease
Por:
Illan-Gaia, I, Lleo, A, Karydas, A, Staffaroni, AM, Zetterberg, H, Sivasankaran, R, Grinberg, LT, Spina, S, Kramer, JH, Ramos, EM, Coppola, G, La Joie, R, Rabinovici, GD, Perry, DC, Gorno-Tempini, ML, Seeley, WW, Miller, BL, Rosen, HJ, Blennow, K, Boxer, AL, Rojas, JC
Publicada:
2 feb 2021
Resumen:
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.
Filiaciones:
Illan-Gaia, I:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Sant Pau Memory Unit,Dept Neurol, Barcelona, Spain
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
Lleo, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Sant Pau Memory Unit,Dept Neurol, Barcelona, Spain
Karydas, A:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Staffaroni, AM:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
UCL, UK Dementia Res Inst, London, England
Sivasankaran, R:
Novartis Inst BioMed Res, Cambridge, MA USA
Grinberg, LT:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Spina, S:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Kramer, JH:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Ramos, EM:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA
Coppola, G:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA
La Joie, R:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Rabinovici, GD:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Perry, DC:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Gorno-Tempini, ML:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Seeley, WW:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Miller, BL:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Rosen, HJ:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Boxer, AL:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Rojas, JC:
Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA
Green Published
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