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Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.
Parkin, Georgia M; Corey-Bloom, Jody; Snell, Chase; Castleton, Jordan; Thomas, Elizabeth A.
Afiliación
  • Parkin GM; Department of Epidemiology, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA. Electronic address: gparkin@hs.uci.edu.
  • Corey-Bloom J; Department of Neurosciences, University of California San Diego, San Diego, CA, USA. Electronic address: jcoreybloom@health.ucsd.edu.
  • Snell C; Department of Neurosciences, University of California San Diego, San Diego, CA, USA. Electronic address: cmsnell@health.ucsd.edu.
  • Castleton J; Department of Neurosciences, University of California San Diego, San Diego, CA, USA. Electronic address: jcastleton@ucsd.edu.
  • Thomas EA; Department of Epidemiology, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA. Electronic address: eathoma1@hs.uci.edu.
Parkinsonism Relat Disord ; 87: 32-38, 2021 06.
Article en En | MEDLINE | ID: mdl-33940564
OBJECTIVE: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy. METHOD: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated. NfL levels were measured using a Meso Scale Discovery assay. RESULTS: Cohorts differed by age. NfL levels differed significantly across diagnostic groups and were significantly correlated with age. Age-adjusted NfL levels were not correlated with clinical measures in either HD or PM cohorts, but were correlated when cohorts were combined. In PM subjects, NfL levels correlated with YTO, probability of onset in 5 years, and years until 60% onset probability. Using ROC analysis, a NfL cut-point of <53.15 pg/ml distinguished HD from control; <74.84 pg/ml distinguished HD from PM. CONCLUSIONS: These findings implicate plasma NfL as a peripheral prognostic marker for premanifest-HD. Notably, we show that significant correlations between NfL and clinical symptoms are detected only when PM + HD subjects are combined, but not within HD subjects alone. To date, prior studies have investigated the clinical usefulness of NfL exclusively in merged PM + HD cohorts. Our data suggests a biasing of these previous correlations, and hence potentially limited usefulness of plasma NfL in monitoring HD symptom progression, for example, in clinical trials.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Neurofilamentos / Enfermedad de Huntington / Síntomas Prodrómicos Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Parkinsonism Relat Disord Asunto de la revista: NEUROLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Neurofilamentos / Enfermedad de Huntington / Síntomas Prodrómicos Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Parkinsonism Relat Disord Asunto de la revista: NEUROLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido