부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]