Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia.
Mov Disord
; 38(9): 1742-1750, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37482941
ABSTRACT
BACKGROUND:
Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1.OBJECTIVE:
The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP.METHODS:
Plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (GFAP) levels were measured in samples from patients and age- and sex-matched controls (NfL n = 46 vs. n = 46; GFAP n = 14 vs. n = 21) using single-molecule array assays. Patients' phenotypes were systematically assessed using the AP-4-HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score.RESULTS:
pNfL levels increased in AP-4-HSP patients, allowing differentiation from controls (Mann-Whitney U test P = 3.0e-10; area under the curve = 0.87 with a 95% confidence interval of 0.80-0.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized-onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann-Whitney U test between two identified clusters P = 2.5e-6). Plasma GFAP levels were unchanged in patients with AP-4-HSP.CONCLUSIONS:
pNfL is a potential disease marker in AP-4-HSP and can help differentiate between phenotypic subgroups. © 2023 International Parkinson and Movement Disorder Society.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spastic Paraplegia, Hereditary
/
Adaptor Protein Complex 4
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mov Disord
Journal subject:
NEUROLOGIA
Year:
2023
Type:
Article
Affiliation country:
United States