TY  - JOUR
AU  - Verde, Federico
AU  - Vávra, Jakub
AU  - Dorst, J.
AU  - Elmas, Zeynep
AU  - Wiesenfarth, Maximilian
AU  - De Gobbi, Anna
AU  - Ratti, Antonia
AU  - Poletti, Barbara
AU  - Tumani, Hayrettin
AU  - Weishaupt, Jochen
AU  - Silani, Vincenzo
AU  - Ticozzi, Nicola
AU  - Otto, Markus
AU  - Ludolph, Albert C
AU  - Oeckl, Patrick
TI  - CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival.
JO  - Journal of neurology, neurosurgery, and psychiatry
VL  - 96
IS  - 12
SN  - 0022-3050
CY  - London
PB  - BMJ Publishing Group
M1  - DZNE-2025-01265
SP  - 1132 - 1143
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Amyotrophic Lateral Sclerosis: cerebrospinal fluid
KW  - Amyotrophic Lateral Sclerosis: mortality
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Biomarkers: cerebrospinal fluid
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Aged
KW  - Retrospective Studies
KW  - Microtubule-Associated Proteins: cerebrospinal fluid
KW  - Disease Progression
KW  - C9orf72 Protein: genetics
KW  - Adult
KW  - Superoxide Dismutase-1: genetics
KW  - ALS (Other)
KW  - CSF (Other)
KW  - MOTOR NEURON DISEASE (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - MAP2 protein, human (NLM Chemicals)
KW  - C9orf72 Protein (NLM Chemicals)
KW  - Superoxide Dismutase-1 (NLM Chemicals)
KW  - C9orf72 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40537251
DO  - DOI:10.1136/jnnp-2025-336208
UR  - https://pub.dzne.de/record/282295
ER  -