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024 7 _ |a 10.1038/s43587-025-01006-w
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037 _ _ |a DZNE-2025-01372
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Caro, Ilana
|0 0000-0003-3075-4682
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245 _ _ |a Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.
260 _ _ |a London
|c 2025
|b Nature Research
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Cerebral 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.
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650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 2 |a Cerebral Small Vessel Diseases: genetics
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: blood
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: diagnostic imaging
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Biomarkers: blood
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Proteogenomics: methods
|2 MeSH
650 _ 2 |a Mendelian Randomization Analysis
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
700 1 _ |a Western, Daniel
|0 0000-0003-3725-9553
|b 1
700 1 _ |a Namba, Shinichi
|0 0000-0002-7486-3146
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700 1 _ |a Sun, Na
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700 1 _ |a Kawaguchi, Shuji
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700 1 _ |a He, Yunye
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700 1 _ |a Fujita, Masashi
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700 1 _ |a Roshchupkin, Gennady
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700 1 _ |a D'Aoust, Tim
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700 1 _ |a Duperron, Marie-Gabrielle
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700 1 _ |a Sargurupremraj, Muralidharan
|0 0000-0003-1684-3750
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700 1 _ |a Tsuchida, Ami
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700 1 _ |a Koido, Masaru
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700 1 _ |a Ahmadi, Marziehsadat
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700 1 _ |a Yang, Chengran
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700 1 _ |a Timsina, Jigyasha
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700 1 _ |a Ibanez, Laura
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700 1 _ |a Matsuda, Koichi
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700 1 _ |a Suzuki, Yutaka
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700 1 _ |a Oda, Yoshiya
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700 1 _ |a Kanai, Akinori
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700 1 _ |a Jandaghi, Pouria
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700 1 _ |a Munter, Markus
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700 1 _ |a Auld, Daniel
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700 1 _ |a Astafeva, Iana
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700 1 _ |a Puerta, Raquel
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700 1 _ |a Rotter, Jerome I
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700 1 _ |a Psaty, Bruce M
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700 1 _ |a Bis, Joshua C
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700 1 _ |a Longstreth, W. T.
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700 1 _ |a Couffinhal, Thierry
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700 1 _ |a García-González, Pablo
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700 1 _ |a Pytel, Vanesa
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700 1 _ |a Marquié, Marta
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700 1 _ |a Cano, Amanda
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700 1 _ |a Boada, Mercè
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700 1 _ |a Joliot, Marc
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700 1 _ |a Lathrop, Mark
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700 1 _ |a Le Grand, Quentin
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700 1 _ |a Launer, Lenore J
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700 1 _ |a Wardlaw, Joanna M
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700 1 _ |a Heiman, Myriam
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700 1 _ |a Ruiz, Agustin
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700 1 _ |a Matthews, Paul M
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700 1 _ |a Seshadri, Sudha
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700 1 _ |a Fornage, Myriam
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700 1 _ |a Adams, Hieab
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700 1 _ |a Mishra, Aniket
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700 1 _ |a Trégouët, David-Alexandre
|0 0000-0001-9084-7800
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700 1 _ |a Okada, Yukinori
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700 1 _ |a Kellis, Manolis
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700 1 _ |a De Jager, Philip L
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700 1 _ |a Tzourio, Christophe
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700 1 _ |a Kamatani, Yoichiro
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700 1 _ |a Matsuda, Fumihiko
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700 1 _ |a Cruchaga, Carlos
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700 1 _ |a Debette, Stéphanie
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773 _ _ |a 10.1038/s43587-025-01006-w
|g Vol. 5, no. 12, p. 2514 - 2531
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