5ff935d98843304f794d601dc57f7462 270497.pdf e594b5e64eeeec72afb728ed38d8ea6ef0c8f727 270497.pdf c2f6aed3db8d65c49434922c8f0f718cdea5555cd5879e476093b5f00ce487c1 270497.pdf Title: Genetic Predisposition to Alzheimer’s Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region Subject: This study investigated whether genetic factors involved in Alzheimer’s disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with BIN1-rs744373, as well as APOE genotypes. We found a significant association of the BIN1-rs744373 polymorphism in the CS subscale (p value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by APOE-4 status (carriers vs. non-carriers), these results remained significant only for 4 carriers (p value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS. Keywords: APOE-4; BIN1-rs744373; enlargement of perivascular spaces; neurogenetics; virchow robin spaces Author: Iacopo Ciampa, Grégory Operto, Carles Falcon, Carolina Minguillon, Manuel Castro de Moura, David Piñeyro, Manel Esteller, Jose Luis Molinuevo, Roderic Guigó, Arcadi Navarro, Juan Domingo Gispert, Natalia Vilor-Tejedor and for the ALFA Study Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu May 27 15:23:50 2021 CEST ModDate: Thu May 27 15:23:50 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1025693 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OLMFWK+URWPalladioL-Ital Type 1 Custom yes yes no 109 0 LGANUC+URWPalladioL-Bold Type 1 Custom yes yes no 110 0 HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 111 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288 0 FPQEVT+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 289 0 FPTOJR+PalatinoLinotype CID TrueType Identity-H yes yes yes 290 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:09:21 CEST RepresentationInformation: 270497.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:04:58 CEST Size: 1025693 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 2 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きちぴづひどちぬぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちひぴどっどばちのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰こぴちのつちひつぜ〴ぜ〰ぐひはぴはっはぬぜ〴ぜ〰ぁばばひはぶちぬび〬ぜ〴ぜ〰げづでどびぴひちぴどはのび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴぜ〴ぜ〰ぃはのびづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぇづのはぴべばどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねちでづぜ〴ぜ〰ぁっぱふどびどぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰げちぴどのでぜ〴ぜ〰はてぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ぐちひぴどっどばちのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰こぴちのつちひつぜ〴ぜ〰ぐひはぴはっはぬぜ〴ぜ〰ぁばばひはぶちぬび〬ぜ〴ぜ〰げづでどびぴひちぴどはのび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴぜ〴ぜ〰ぃはのびづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぇづのはぴべばどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねちでづぜ〴ぜ〰ぁっぱふどびどぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰げちぴどのでぜ〴ぜ〰はてぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちのつちひつぜ〴ぜ〰ぐひはぴはっはぬぜ〴ぜ〰ぁばばひはぶちぬび〬ぜ〴ぜ〰げづでどびぴひちぴどはのび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴぜ〴ぜ〰ぃはのびづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぇづのはぴべばどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねちでづぜ〴ぜ〰ぁっぱふどびどぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰げちぴどのでぜ〴ぜ〰はてぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぇづのはぴべばどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねちでづぜ〴ぜ〰ぁっぱふどびどぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰げちぴどのでぜ〴ぜ〰はてぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぉねちでづぜ〴ぜ〰ぁっぱふどびどぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰げちぴどのでぜ〴ぜ〰はてぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰こちねばぬづぜ〴ぜ〰いづびっひどばぴどぶづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぁぐくぅぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰あぉぎ〱〭ひび〷〴〴〳〷〳ぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぁでづ〭いづばづのつづのぴぜ〴ぜ〰ぅててづっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: こちねばぬづぜ〴ぜ〰いづびっひどばぴどぶづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぁぐくぅぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰あぉぎ〱〭ひび〷〴〴〳〷〳ぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぁでづ〭いづばづのつづのぴぜ〴ぜ〰ぅててづっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぁぐくぅぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰あぉぎ〱〭ひび〷〴〴〳〷〳ぜ〴ぜ〰ちのつぜ〴ぜ〰づぐざこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぁでづ〭いづばづのつづのぴぜ〴ぜ〰ぅててづっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: 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