R869c mutation in molecular motor kif17 gene is involved in dementia with lewy bodies

Orly Goldstein, Mali Gana-Weisz, Tamara Shiner, Reut Attar, Yael Mordechai, Yedael Y. Waldman, Anat Bar-Shira, Avner Thaler, Tanya Gurevich, Anat Mirelman, Nir Giladi, Avi Orr-Urtreger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Introduction: The: GBA-N370S mutation is one of the most frequent risk factors for dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). We looked for genetic variations that contribute to the outcome in N370S-carriers, whether PD or DLB. Methods: Whole-genome sequencing of 95 Ashkenazi-N370S-carriers affected with either DLB (n = 19) or PD (n = 76) was performed, and 564 genes related to dementia and PD analyzed. Results: We identified enrichment of linked alleles in PINK1 locus in DLB patients (false discovery rate P = .0412). Haplotype analysis delineated 1.8 Mb interval encom-passing 29 genes and 87 unique variants, of them, KIF17-R869C received the high-est functional prediction score (Combined Annotation Dependent Depletion = 34). Its frequency was significantly higher in 26 DLB-N370S-carriers compared to 140 PD-N370S-carriers (odds ratio [OR] = 33.4 P = .001, and OR = 70.2 when only heterozy-gotes were included). Discussion: Because KIF17 was shown to be important for learning and memory in mice, our data further suggest, for the first time, its involvement in DLB, and possibly in human dementia.

Original languageEnglish
Article numbere12143
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Issue number1
StatePublished - 2021


FundersFunder number
Chaya Charitable Fund


    • Dementia with Lewy bodies
    • GBA
    • KIF17
    • Parkinson’s disease
    • Risk allele


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