Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease.
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ABSTRACT: Introduction
Alexander disease (AxD) is a rare leukodystrophy caused by dominant gain-of-function mutations in the gene encoding the astrocyte intermediate filament, glial fibrillary acidic protein (GFAP). However, there is an urgent need for biomarkers to assist in monitoring not only the progression of disease but also the response to treatment. GFAP is the obvious candidate for such a biomarker, as it is measurable in body fluids that are readily accessible for biopsy, namely cerebrospinal fluid and blood. However, in the case of ASOs, the treatment that is furthest in development, GFAP is the target of therapy and presumably would go down independent of disease status. Hence, there is a critical need for biomarkers that are not directly affected by the treatment strategy.Methods
We explored the potential utility of biomarkers currently being studied in other neurodegenerative diseases and injuries, specifically neurofilament light protein (NfL), phosphorylated forms of tau, and amyloid-β peptides (Aβ42/40).Results and conclusions
Here, we report that GFAP is elevated in plasma of all age groups afflicted by AxD, including those with adult onset. NfL and p-tau are also elevated, but to a much lesser extent than GFAP. In contrast, the levels of Aß40 and Aß42 are not altered in AxD.
SUBMITTER: Ashton NJ
PROVIDER: S-EPMC11305938 | biostudies-literature | 2024 Sep
REPOSITORIES: biostudies-literature
Publications
Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease.
Ashton Nicholas J NJ Di Molfetta Guglielmo G Tan Kübra K Blennow Kaj K Zetterberg Henrik H Messing Albee A
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 20240401 9
<h4>Introduction</h4>Alexander disease (AxD) is a rare leukodystrophy caused by dominant gain-of-function mutations in the gene encoding the astrocyte intermediate filament, glial fibrillary acidic protein (GFAP). However, there is an urgent need for biomarkers to assist in monitoring not only the progression of disease but also the response to treatment. GFAP is the obvious candidate for such a biomarker, as it is measurable in body fluids that are readily accessible for biopsy, namely cerebros ...[more]
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