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000282911 0247_ $$2doi$$a10.1038/s43587-025-01006-w
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000282911 037__ $$aDZNE-2025-01372
000282911 041__ $$aEnglish
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000282911 1001_ $$00000-0003-3075-4682$$aCaro, Ilana$$b0
000282911 245__ $$aProteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.
000282911 260__ $$aLondon$$bNature Research$$c2025
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000282911 520__ $$aCerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences between fluids. The proteins are enriched in pathways related to the extracellular matrix, immune response and microglial activity. Many also associate with stroke and dementia, and several correspond to existing drug targets. Together, these findings reveal a robust biological fingerprint of cSVD and highlight opportunities for biomarker and drug discovery and repositioning.
000282911 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0
000282911 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000282911 650_7 $$2NLM Chemicals$$aBiomarkers
000282911 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: genetics
000282911 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: cerebrospinal fluid
000282911 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: blood
000282911 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: diagnostic imaging
000282911 650_2 $$2MeSH$$aHumans
000282911 650_2 $$2MeSH$$aBiomarkers: blood
000282911 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000282911 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000282911 650_2 $$2MeSH$$aProteogenomics: methods
000282911 650_2 $$2MeSH$$aMendelian Randomization Analysis
000282911 650_2 $$2MeSH$$aMale
000282911 650_2 $$2MeSH$$aFemale
000282911 650_2 $$2MeSH$$aAged
000282911 7001_ $$00000-0003-3725-9553$$aWestern, Daniel$$b1
000282911 7001_ $$00000-0002-7486-3146$$aNamba, Shinichi$$b2
000282911 7001_ $$aSun, Na$$b3
000282911 7001_ $$00000-0002-4045-6518$$aKawaguchi, Shuji$$b4
000282911 7001_ $$00000-0001-8581-7826$$aHe, Yunye$$b5
000282911 7001_ $$aFujita, Masashi$$b6
000282911 7001_ $$aRoshchupkin, Gennady$$b7
000282911 7001_ $$aD'Aoust, Tim$$b8
000282911 7001_ $$aDuperron, Marie-Gabrielle$$b9
000282911 7001_ $$00000-0003-1684-3750$$aSargurupremraj, Muralidharan$$b10
000282911 7001_ $$aTsuchida, Ami$$b11
000282911 7001_ $$00000-0002-0348-0666$$aKoido, Masaru$$b12
000282911 7001_ $$aAhmadi, Marziehsadat$$b13
000282911 7001_ $$00000-0003-4577-5590$$aYang, Chengran$$b14
000282911 7001_ $$00000-0003-4794-9187$$aTimsina, Jigyasha$$b15
000282911 7001_ $$aIbanez, Laura$$b16
000282911 7001_ $$aMatsuda, Koichi$$b17
000282911 7001_ $$00000-0003-4852-1879$$aSuzuki, Yutaka$$b18
000282911 7001_ $$aOda, Yoshiya$$b19
000282911 7001_ $$aKanai, Akinori$$b20
000282911 7001_ $$aJandaghi, Pouria$$b21
000282911 7001_ $$aMunter, Markus$$b22
000282911 7001_ $$00000-0002-9486-1105$$aAuld, Daniel$$b23
000282911 7001_ $$aAstafeva, Iana$$b24
000282911 7001_ $$00000-0002-1191-5893$$aPuerta, Raquel$$b25
000282911 7001_ $$00000-0001-7191-1723$$aRotter, Jerome I$$b26
000282911 7001_ $$00000-0002-7278-2190$$aPsaty, Bruce M$$b27
000282911 7001_ $$00000-0002-3409-1110$$aBis, Joshua C$$b28
000282911 7001_ $$aLongstreth, W. T.$$b29
000282911 7001_ $$aCouffinhal, Thierry$$b30
000282911 7001_ $$00000-0003-0125-5403$$aGarcía-González, Pablo$$b31
000282911 7001_ $$aPytel, Vanesa$$b32
000282911 7001_ $$00000-0002-0660-0950$$aMarquié, Marta$$b33
000282911 7001_ $$aCano, Amanda$$b34
000282911 7001_ $$00000-0003-2617-3009$$aBoada, Mercè$$b35
000282911 7001_ $$00000-0001-7792-308X$$aJoliot, Marc$$b36
000282911 7001_ $$aLathrop, Mark$$b37
000282911 7001_ $$0P:(DE-2719)9002736$$aLe Grand, Quentin$$b38$$udzne
000282911 7001_ $$00000-0002-3238-7612$$aLauner, Lenore J$$b39
000282911 7001_ $$00000-0002-9812-6642$$aWardlaw, Joanna M$$b40
000282911 7001_ $$aHeiman, Myriam$$b41
000282911 7001_ $$00000-0003-2633-2495$$aRuiz, Agustin$$b42
000282911 7001_ $$aMatthews, Paul M$$b43
000282911 7001_ $$00000-0001-6135-2622$$aSeshadri, Sudha$$b44
000282911 7001_ $$00000-0003-0677-8158$$aFornage, Myriam$$b45
000282911 7001_ $$aAdams, Hieab$$b46
000282911 7001_ $$aMishra, Aniket$$b47
000282911 7001_ $$00000-0001-9084-7800$$aTrégouët, David-Alexandre$$b48
000282911 7001_ $$00000-0002-0311-8472$$aOkada, Yukinori$$b49
000282911 7001_ $$00000-0001-7113-9630$$aKellis, Manolis$$b50
000282911 7001_ $$00000-0002-8057-2505$$aDe Jager, Philip L$$b51
000282911 7001_ $$00000-0002-6517-2984$$aTzourio, Christophe$$b52
000282911 7001_ $$00000-0001-8748-5597$$aKamatani, Yoichiro$$b53
000282911 7001_ $$aMatsuda, Fumihiko$$b54
000282911 7001_ $$00000-0002-0276-2899$$aCruchaga, Carlos$$b55
000282911 7001_ $$00000-0001-8675-7968$$aDebette, Stéphanie$$b56
000282911 773__ $$0PERI:(DE-600)3029419-8$$a10.1038/s43587-025-01006-w$$gVol. 5, no. 12, p. 2514 - 2531$$n12$$p2514 - 2531$$tNature aging$$v5$$x2662-8465$$y2025
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