Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.

Autor:	Hristovska I; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Binette AP; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Kumar A; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Gaiteri C; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.; Rush University Alzheimer's Disease Center, Rush University, Chicago IL, USA., Karlsson L; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Strandberg O; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Janelidze S; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., van Westen D; Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University.; Imaging and Function, Skåne University Hospital, Lund, Sweden., Stomrud E; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, Malmö, Sweden., Palmqvist S; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, Malmö, Sweden., Ossenkoppele R; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands., Mattsson-Carlgren N; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Department of Neurology, Skåne University Hospital, Lund, Sweden.; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden., Vogel JW; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Department of Clinical Sciences, Malmö, SciLifeLab, Lund University, Lund, Sweden., Hansson O; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Jun 10. Date of Electronic Publication: 2024 Jun 10.
DOI:	10.1101/2024.06.10.24308599
Abstrakt:	The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 living patients, and validated WML-associated proteins in three additional datasets. Proteins indicative of extracellular matrix dysregulation and vascular remodeling, including ELN, POSTN, CCN2 and MMP12 were elevated across all cSVD manifestations, with MMP12 emerging as an early cSVD indicator. cSVD-associated proteins formed a co-abundance network linked to metabolism and enriched in endothelial and arterial smooth muscle cells, showing elevated levels at early disease manifestations. Later disease stages involved changes in microglial proteins, associated with longitudinal WML progression, and changes in neuronal proteins mediating WML-associated cognitive decline. These findings provide an atlas of novel cSVD biomarkers and a promising roadmap for the next generation of cSVD therapeutics. Competing Interests: OH has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, C2N Diagnostics, Eli Lilly, Eisai, Fujirebio, GE Healthcare, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Alzpath, BioArctic, Biogen, Bristol Meyer Squibb, Cerveau, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. SP has acquired research support (for the institution) from ki elements/ADDF. In the past 2 years, he has received consultancy/speaker fees from BioArtic, Biogen, Lilly and Roche. The remaining others declare no competing interests.
Databáze:	MEDLINE
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