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000281531 1001_ $$aReid, Madigan M$$b0
000281531 245__ $$aHuman brain vascular multi-omics elucidates disease-risk associations.
000281531 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000281531 520__ $$aCerebrovascular dysfunction underlies many neurological disorders, yet how genetic variants in brain vascular cells drive disease risk remains unknown. We developed MultiVINE-seq to simultaneously profile RNA and chromatin accessibility in vascular, perivascular, and immune cells from 30 human brains. Mapping genome-wide association study (GWAS) data to our multi-omic atlas linked thousands of GWAS disease-risk variants to target cell types and genes, including 2,605 previously unmapped. We found cerebrovascular and neurodegenerative disease variants have distinct mechanisms: cerebrovascular disease variants disrupt extracellular matrix genes in endothelial, mural, and fibroblast cells important for vessel structural integrity, while Alzheimer's disease (AD) variants dysregulate inflammatory adaptor proteins in endothelial and immune cells. Notably, a lead AD variant enhances PTK2B expression in brain CD8 T cells, providing genetic evidence for adaptive immunity in AD pathogenesis. This work provides a key resource for interpreting genetic risk and reveals how variants in vascular cells drive divergent pathogenic mechanisms across neurological diseases.
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000281531 650_7 $$2Other$$aAlzheimer's disease
000281531 650_7 $$2Other$$aT cell
000281531 650_7 $$2Other$$abrain vasculature
000281531 650_7 $$2Other$$acerebrovascular disease
000281531 650_7 $$2Other$$amacrophage
000281531 650_7 $$2Other$$amicroglia
000281531 650_7 $$2Other$$aneurodegenerative disease
000281531 650_7 $$2Other$$anon-coding disease-risk variants
000281531 650_7 $$2Other$$asingle-cell multi-omics
000281531 650_7 $$2Other$$astroke
000281531 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aFocal Adhesion Kinase 2
000281531 650_2 $$2MeSH$$aHumans
000281531 650_2 $$2MeSH$$aGenome-Wide Association Study
000281531 650_2 $$2MeSH$$aBrain: blood supply
000281531 650_2 $$2MeSH$$aBrain: metabolism
000281531 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000281531 650_2 $$2MeSH$$aGenetic Predisposition to Disease: genetics
000281531 650_2 $$2MeSH$$aCerebrovascular Disorders: genetics
000281531 650_2 $$2MeSH$$aFemale
000281531 650_2 $$2MeSH$$aMale
000281531 650_2 $$2MeSH$$aFocal Adhesion Kinase 2: genetics
000281531 650_2 $$2MeSH$$aFocal Adhesion Kinase 2: metabolism
000281531 650_2 $$2MeSH$$aMultiomics
000281531 7001_ $$aMenon, Shreya$$b1
000281531 7001_ $$aLiu, Hao$$b2
000281531 7001_ $$aZhou, Haoyue$$b3
000281531 7001_ $$aHu, Zhirui$$b4
000281531 7001_ $$aFrerich, Simon$$b5
000281531 7001_ $$aDing, Bella$$b6
000281531 7001_ $$aOveisgharan, Shahram$$b7
000281531 7001_ $$aZhang, Zimo$$b8
000281531 7001_ $$aNelson, Sophia$$b9
000281531 7001_ $$aApolonio, Amanda$$b10
000281531 7001_ $$aBennett, David A$$b11
000281531 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b12$$udzne
000281531 7001_ $$aPollard, Katherine S$$b13
000281531 7001_ $$aCorces, M Ryan$$b14
000281531 7001_ $$aYang, Andrew C$$b15
000281531 773__ $$0PERI:(DE-600)2001944-0$$a10.1016/j.neuron.2025.07.001$$gVol. 113, no. 19, p. 3143 - 3161.e5$$n19$$p3143 - 3161.e5$$tNeuron$$v113$$x0896-6273$$y2025
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