Journal Article

DZNE-2026-00419

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Homozygosity for the C allele at UNC13A rs12608932 seems to compromise cognition in ALS independently of the cognitive domains.

Lehto, A. (First author)DZNE* ; Zapf, A. ; Hermann, A.DZNE* ; Machts, J. ; Vielhaber, S.DZNE* ; Koppenbrink, J.DZNE* ; Edbauer, D.DZNE* ; Kasper, E.Extern* ; Prudlo, J. (Last author)DZNE*

2026
Taylor Francis Group Abingdon

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Please use a persistent id in citations: doi:10.1080/21678421.2025.2608238

Abstract: The common single nucleotide polymorphism (SNP) rs12608932 located at a cryptic splice in the UNC13A gene has been reported to modify the clinical phenotype of ALS, but it is unclear whether homozygosity for the C-allele at UNC13A rs12608932 modifies specific domains of cognition in ALS. We analyzed retrospective data from a German cohort and found that the proportion of cognitively or behaviorally impaired patients was higher in the high-risk group of homozygous C-allele carriers. Patients with C/C alleles had lower scores than controls on verbal fluency, executive functioning, and delayed memory recall, but did not differ significantly from other ALS genotypes. Furthermore, informant ratings suggested higher disinhibition in the C/C carriers. These findings indicate that the C/C risk variant of UNC13A rs12608932 may contribute to general cognitive vulnerability rather than domain-specific deficit.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Amyotrophic Lateral Sclerosis: complications (MeSH) ; Amyotrophic Lateral Sclerosis: psychology (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Aged (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Homozygote (MeSH) ; Retrospective Studies (MeSH) ; Alleles (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Cognitive Dysfunction: etiology (MeSH) ; Cognition: physiology (MeSH) ; Adult (MeSH) ; Neuropsychological Tests (MeSH) ; Cohort Studies (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Germany (MeSH) ; Amyotrophic Lateral Sclerosis ; UNC13A ; cognition ; rs12608932 ; Nerve Tissue Proteins

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
2. Translational Neurodegeneration (AG Hermann)
3. Cell Biology of Neurodegeneration (AG Edbauer)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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