Journal article
Associations between prognostic index scores and plasma neurofilament light in Huntington's disease
Parkinsonism & related disorders, Vol.97, pp.25-28
04/2022
DOI: 10.1016/j.parkreldis.2022.02.023
PMCID: PMC9127124
PMID: 35276585
Abstract
The inclusion of premanifest Huntington's Disease (Pre-HD) subjects in clinical trials necessitates selecting those who are near transition to manifest Huntington's disease (Man-HD). We previously determined that plasma neurofilament light (NfL) levels are significantly correlated with predicted years to Man-HD onset, using established formulae. Recently, a new normalized prognostic index (PIN) score for predicting Pre-HD disease progression has been validated. Our objective was to determine whether plasma NfL levels are similarly associated with PIN score and PIN score-derived years to Man-HD onset (PIN-YTO).
112 individuals (46 Pre-HD, 66 Man-HD) underwent blood sample collection and clinical assessment, inclusive of the Symbol Digit Modalities Test and Unified Huntington's Disease Rating Scale Total Motor Score. Plasma NfL levels were measured using a Meso Scale Discovery assay.
Pre-HD and Man-HD cohorts differed by age (p < .0001), and CAG repeat number (p = .004), but not education level or gender. Plasma NfL levels were significantly correlated with PIN scores (r = 0.69, p < .0001) and PIN-YTO (r = −0.69, p < .0001). Plasma NfL levels were similarly correlated with predicted years to onset scores determined using Langbehn and colleague's formula (r = −0.68, p < .0001). All significant correlations endured corrections for age and CAG repeat number. A plasma NfL cut-point of <45.0 pg/ml distinguished Pre-HD participants >10 predicted years from Man-HD onset, compared to those ≤10 predicted years.
We have extensively shown that plasma NfL levels are associated with predicted years to manifest HD onset in Pre-HD participants, and present a plasma NfL cut-point that may help exclude far-from-onset Pre-HD patients from clinical trials.
•Plasma NfL is correlated with the normalized prognostic index (PIN) score.•Plasma NfL correlated with PIN-derived predicted years to manifest HD onset (YTO).•A plasma NfL cut-point of <45.0 pg/ml identifies premanifest HD far from HD onset.•Associations mirrored those previously observed using Langbehn et al.’s YTO formula.•Plasma NfL is associated with YTO but not factors unique to the PIN.
Details
- Title: Subtitle
- Associations between prognostic index scores and plasma neurofilament light in Huntington's disease
- Creators
- Georgia M. Parkin - University of California, IrvineJody Corey-Bloom - University of California San DiegoJeffrey D. Long - University of IowaChase Snell - University of California San DiegoHaileigh Smith - University of California San DiegoElizabeth A. Thomas - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Parkinsonism & related disorders, Vol.97, pp.25-28
- DOI
- 10.1016/j.parkreldis.2022.02.023
- PMID
- 35276585
- PMCID
- PMC9127124
- NLM abbreviation
- Parkinsonism Relat Disord
- ISSN
- 1353-8020
- eISSN
- 1873-5126
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: NS111655, P50 AG005131; DOI: 10.13039/100007911, name: University of California, San Diego
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Psychiatry; Biostatistics
- Record Identifier
- 9984280841602771
Metrics
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