Journal Article

DZNE-2025-01265

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival.

Verde, F. ; Vávra, J. (First author)DZNE* ; Dorst, J.DZNE* ; Elmas, Z. ; Wiesenfarth, M. ; De Gobbi, A. ; Ratti, A. ; Poletti, B. ; Tumani, H.DZNE* ; Weishaupt, J. ; Silani, V. ; Ticozzi, N. ; Otto, M. ; Ludolph, A. C.DZNE* ; Oeckl, P. (Last author)DZNE*

2025
BMJ Publishing Group London

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Please use a persistent id in citations: doi:10.1136/jnnp-2025-336208

Abstract: Previous proteomic work has identified the somatodendritic protein MAP2 as a new candidate cerebrospinal fluid (CSF) biomarker for amyotrophic lateral sclerosis (ALS).We measured CSF levels of MAP2 and neurofilament light chain (NFL) in a retrospective cohort of 251 patients with ALS and 108 neurological controls (NCs).Patients with ALS had a higher median CSF MAP2 level compared with NCs, leading to an area under the curve (AUC) of 0.7080 (p<0.0001). They also had a higher median CSF NFL level (p<0.0001), resulting in an excellent diagnostic performance (AUC=0.9641; p<0.0001). Among patients with ALS, CSF MAP2 correlated with disease progression rate (DPR) (r=0.3099; p<0.0001) and was negatively associated with survival (HR=3.174). CSF NFL also correlated with DPR (r=0.4936; p<0.0001) and was negatively associated with survival (HR=2.759). The association of MAP2 with DPR was independent from NFL (p=0.0037). Stratifying patients based on median levels of both biomarkers resulted in significant differences in median survival times (low NFL/low MAP2, 66 months; high NFL/low MAP2 and vice versa, 35 months; high NFL/high MAP2, 26 months; p<0.0001). MAP2 was also associated with genetic status in patients with ALS, as patients with no mutations in C9ORF72 or in SOD1, as well as C9ORF72-positive ones, had higher median levels compared with NCs (p<0.0001), while patients with SOD1 mutations did not significantly differ from NCs (p>0.9999).Our study shows that the somatodendritic protein MAP2 is a promising candidate CSF biomarker for ALS.

Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: cerebrospinal fluid (MeSH) ; Amyotrophic Lateral Sclerosis: mortality (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Aged (MeSH) ; Retrospective Studies (MeSH) ; Microtubule-Associated Proteins: cerebrospinal fluid (MeSH) ; Disease Progression (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Adult (MeSH) ; Superoxide Dismutase-1: genetics (MeSH) ; ALS ; CSF ; MOTOR NEURON DISEASE ; Biomarkers ; Neurofilament Proteins ; neurofilament protein L ; Microtubule-Associated Proteins ; MAP2 protein, human ; C9orf72 Protein ; Superoxide Dismutase-1 ; C9orf72 protein, human

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Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)
2. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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