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@ARTICLE{Caro:282911,
      author       = {Caro, Ilana and Western, Daniel and Namba, Shinichi and
                      Sun, Na and Kawaguchi, Shuji and He, Yunye and Fujita,
                      Masashi and Roshchupkin, Gennady and D'Aoust, Tim and
                      Duperron, Marie-Gabrielle and Sargurupremraj, Muralidharan
                      and Tsuchida, Ami and Koido, Masaru and Ahmadi, Marziehsadat
                      and Yang, Chengran and Timsina, Jigyasha and Ibanez, Laura
                      and Matsuda, Koichi and Suzuki, Yutaka and Oda, Yoshiya and
                      Kanai, Akinori and Jandaghi, Pouria and Munter, Markus and
                      Auld, Daniel and Astafeva, Iana and Puerta, Raquel and
                      Rotter, Jerome I and Psaty, Bruce M and Bis, Joshua C and
                      Longstreth, W. T. and Couffinhal, Thierry and
                      García-González, Pablo and Pytel, Vanesa and Marquié,
                      Marta and Cano, Amanda and Boada, Mercè and Joliot, Marc
                      and Lathrop, Mark and Le Grand, Quentin and Launer, Lenore J
                      and Wardlaw, Joanna M and Heiman, Myriam and Ruiz, Agustin
                      and Matthews, Paul M and Seshadri, Sudha and Fornage, Myriam
                      and Adams, Hieab and Mishra, Aniket and Trégouët,
                      David-Alexandre and Okada, Yukinori and Kellis, Manolis and
                      De Jager, Philip L and Tzourio, Christophe and Kamatani,
                      Yoichiro and Matsuda, Fumihiko and Cruchaga, Carlos and
                      Debette, Stéphanie},
      title        = {{P}roteogenomics in cerebrospinal fluid and plasma reveals
                      new biological fingerprint of cerebral small vessel
                      disease.},
      journal      = {Nature aging},
      volume       = {5},
      number       = {12},
      issn         = {2662-8465},
      address      = {London},
      publisher    = {Nature Research},
      reportid     = {DZNE-2025-01372},
      pages        = {2514 - 2531},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Cerebral Small Vessel Diseases: genetics / Cerebral Small
                      Vessel Diseases: cerebrospinal fluid / Cerebral Small Vessel
                      Diseases: blood / Cerebral Small Vessel Diseases: diagnostic
                      imaging / Humans / Biomarkers: blood / Biomarkers:
                      cerebrospinal fluid / Magnetic Resonance Imaging /
                      Proteogenomics: methods / Mendelian Randomization Analysis /
                      Male / Female / Aged / Biomarkers (NLM Chemicals)},
      cin          = {AG Breteler},
      ddc          = {610},
      cid          = {I:(DE-2719)1012001},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41266628},
      doi          = {10.1038/s43587-025-01006-w},
      url          = {https://pub.dzne.de/record/282911},
}