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- W2893332322 abstract "The majority (90%–95%) of amyotrophic lateral sclerosis (ALS) is sporadic, and ∼50% of patients develop symptoms of frontotemporal degeneration (FTD) associated with shorter survival. The genetic polymorphism rs12608932 in UNC13A confers increased risk of sporadic ALS and sporadic FTD and modifies survival in ALS. Here, we evaluate whether rs12608932 is also associated with frontotemporal disease in sporadic ALS. We identified reduced cortical thickness in sporadic ALS with T1-weighted magnetic resonance imaging (N = 109) relative to controls (N = 113), and observed that minor allele (C) carriers exhibited greater reduction of cortical thickness in the dorsal prefrontal, ventromedial prefrontal, anterior temporal, and middle temporal cortices and worse performance on a frontal lobe–mediated cognitive test (reverse digit span). In sporadic ALS with autopsy data (N = 102), minor allele homozygotes exhibited greater burden of phosphorylated tar DNA-binding protein-43 kda (TDP-43) pathology in the middle frontal, middle temporal, and motor cortices. Our findings demonstrate converging evidence that rs12608932 may modify frontotemporal disease in sporadic ALS and suggest that rs12608932 may function as a prognostic indicator and could be used to define patient endophenotypes in clinical trials." @default.
- W2893332322 created "2018-10-05" @default.
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- W2893332322 date "2019-01-01" @default.
- W2893332322 modified "2023-10-16" @default.
- W2893332322 title "UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis" @default.
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- W2893332322 doi "https://doi.org/10.1016/j.neurobiolaging.2018.09.031" @default.
- W2893332322 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6251755" @default.
- W2893332322 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30368160" @default.
- W2893332322 hasPublicationYear "2019" @default.
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