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Patients' phenotypes were systematically assessed using the AP\u20104\u2010HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>pNfL levels increased in AP\u20104\u2010HSP patients, allowing differentiation from controls (Mann\u2010Whitney <jats:italic>U<\/jats:italic> test: <jats:italic>P<\/jats:italic>\u2009=\u20093.0e\u201010; area under the curve\u2009=\u20090.87 with a 95% confidence interval of 0.80\u20130.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized\u2010onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann\u2010Whitney <jats:italic>U<\/jats:italic> test between two identified clusters: <jats:italic>P<\/jats:italic>\u2009=\u20092.5e\u20106). Plasma GFAP levels were unchanged in patients with AP\u20104\u2010HSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>pNfL is a potential disease marker in AP\u20104\u2010HSP and can help differentiate between phenotypic subgroups. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29524","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T03:57:35Z","timestamp":1689998255000},"page":"1742-1750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex <scp>4\u2010Related<\/scp> Hereditary Spastic Paraplegia"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1420-9775","authenticated-orcid":false,"given":"Julian E.","family":"Alecu","sequence":"first","affiliation":[{"name":"Department of Neurology and F.M. 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Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Neurology and F.M. 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