Reference : Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups
Kaivola, Karri []
Shah, Zalak []
Chia, Ruth []
International LBD Genomics Consortium []
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core >]
Krüger, Rejko mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Scholz, Sonja W. []
Brain: a Journal of Neurology
Oxford University Press
Yes (verified by ORBilu)
United Kingdom
[en] Dementia ; Lewy body dementia ; APOE ; Alzheimer's disease ; copathology
[en] The APOE locus is strongly associated with risk for developing Alzheimer’s disease and dementia with Lewy bodies (DLB). In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2,466 DLB cases versus 2,928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for DLB in patients without APOE ε4 (p = 6.58 x 10−9, OR = 3.41, 95% CI = 2.25–5.17), but not with DLB with APOE ε4 (p = 0.034, OR = 1.87, 95%, 95% CI = 1.05–3.37). We then divided 495 neuropathologically examined DLB cases into three groups based on the extent of concomitant Alzheimer’s disease co-pathology: pure DLB (n = 88), DLB with intermediate Alzheimer’s disease co-pathology (DLB + iAD, n = 66), and DLB with high Alzheimer’s disease co-pathology (DLB + AD, n = 341). In each group, we tested the association of the APOE ε4 against the 2,928 neurologically healthy controls. Our examination found that APOE ε4 was associated with DLB + AD (p = 1.29x10−32, OR = 4.25, 95% CI = 3.35–5.39) and DLB + iAD (p = 0.0011, OR = 2.31, 95% CI = 1.40–3.83), but not with pure DLB (p = 0.31, OR = 0.75, 95% CI = 0.43–1.30). In conclusion, though deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure DLB, but rather implicate GBA as the main risk gene for the pure DLB subgroup.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Fonds National de la Recherche - FnR
Researchers ; Professionals ; Students ; General public
FnR ; FNR11264123 > Rejko Krüger > NCER-PD > Ncer-pd > 01/01/2015 > 30/11/2020 > 2015

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