Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank.
Amyotroph Lateral Scler Frontotemporal Degener
; 25(1-2): 170-176, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38013452
ABSTRACT
OBJECTIVE:
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized.METHODS:
We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS. We applied logistic and Cox proportional hazards regression to compare cases to 42,752 population-based and 948 age and sex-matched controls. Genetic information was obtained from exome and genotype array data.Results andConclusions:
We observed that NfL was 1.42-fold higher in cases vs population-based controls. At two to three years pre-diagnosis, NfL levels in patients exceeded the 95th percentile of age and sex-matched controls. A time-to-diagnosis analysis showed that a 2-fold increase in NfL levels was associated with a 3.4-fold risk of diagnosis per year, with NfL being most predictive of case status at two years (AUC = 0.96). Participants with genetic variation that might put them at risk for familial disease (N = 46) did not show a different pattern of association than those without (N = 191).DISCUSSION:
Our findings show that NfL is elevated and discriminative of future ALS diagnosis up to two years prior to diagnosis in patients with and without genetic risk variants.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Esclerose Lateral Amiotrófica
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article