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DOI 10.1038/s43587-025-01006-w

Медицинская библиотека · Nature aging · 2025

Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.

Caro Ilana, Western Daniel, Namba Shinichi, Sun Na, Kawaguchi Shuji, He Yunye, Fujita Masashi, Roshchupkin Gennady, D'Aoust Tim, Duperron Marie-Gabrielle, Sargurupremraj Muralidharan, Tsuchida Ami, Koido Masaru, Ahmadi Marziehsadat, Yang Chengran, Timsina Jigyasha, Ibanez Laura, Matsuda Koichi, Suzuki Yutaka, Oda Yoshiya, Kanai Akinori, Jandaghi Pouria, Munter Markus, Auld Daniel, Astafeva Iana, Puerta Raquel, Rotter Jerome I, Psaty Bruce M, Bis Joshua C, Longstreth W T, Couffinhal Thierry, García-González Pablo, Pytel Vanesa, Marquié Marta, Cano Amanda, Boada Mercè, Joliot Marc, Lathrop Mark, Le Grand Quentin, Launer Lenore J, Wardlaw Joanna M, Heiman Myriam, Ruiz Agustin, Matthews Paul M, Seshadri Sudha, Fornage Myriam, Adams Hieab, Mishra Aniket, Trégouët David-Alexandre, Okada Yukinori, Kellis Manolis, De Jager Philip L, Tzourio Christophe, Kamatani Yoichiro, Matsuda Fumihiko, Cruchaga Carlos, Debette Stéphanie

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Аннотация

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.

Для цитирования: Caro Ilana, Western Daniel, Namba Shinichi, Sun Na, Kawaguchi Shuji, He Yunye, Fujita Masashi, Roshchupkin Gennady, D'Aoust Tim, Duperron Marie-Gabrielle, Sargurupremraj Muralidharan, Tsuchida Ami, Koido Masaru, Ahmadi Marziehsadat, Yang Chengran, Timsina Jigyasha, Ibanez Laura, Matsuda Koichi, Suzuki Yutaka, Oda Yoshiya, Kanai Akinori, Jandaghi Pouria, Munter Markus, Auld Daniel, Astafeva Iana, Puerta Raquel, Rotter Jerome I, Psaty Bruce M, Bis Joshua C, Longstreth W T, Couffinhal Thierry, García-González Pablo, Pytel Vanesa, Marquié Marta, Cano Amanda, Boada Mercè, Joliot Marc, Lathrop Mark, Le Grand Quentin, Launer Lenore J, Wardlaw Joanna M, Heiman Myriam, Ruiz Agustin, Matthews Paul M, Seshadri Sudha, Fornage Myriam, Adams Hieab, Mishra Aniket, Trégouët David-Alexandre, Okada Yukinori, Kellis Manolis, De Jager Philip L, Tzourio Christophe, Kamatani Yoichiro, Matsuda Fumihiko, Cruchaga Carlos, Debette Stéphanie. Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.. Nature aging. 2025. DOI: 10.1038/s43587-025-01006-w.

Предметные рубрики MeSH

Cerebral Small Vessel DiseasesHumansBiomarkersMagnetic Resonance ImagingProteogenomicsMendelian Randomization AnalysisMaleFemaleAged
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