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However, CeVD frequently coexists with AD, and both conditions fall within the spectrum of vascular cognitive impairment (VCI). Notably, chronic neuroinflammation is a shared mechanistic link between AD and VaD. Inflammasomes, multi-protein complexes that sense cellular damage and orchestrate inflammatory responses, have been implicated in preclinical models of both diseases. However, their translational potential in the clinical setting remains underexplored. Here, we investigate the inflammasome adaptor protein, apoptosis associated speck-like protein containing a CARD (ASC), as a novel serum biomarker for CeVD, cognitive decline and VCI progression. A total of 531 participants (123 non-cognitively impaired, 208 cognitive impaired, no dementia and 200 with dementia) were included from a Singapore-based clinical cohort. All subjects underwent comprehensive clinical, neuropsychological and neuroimaging assessments. Serum samples were collected, and ASC was measured using a microfluidics immunoassay platform. Compared to controls, serum ASC levels were increased in the VCI clinical subgroups, namely, cognitive impaired, no dementia with CeVD, AD with CeVD and VaD. Multivariate analyses using CeVD neuroimaging markers showed associations between serum ASC and white matter hyperintensities, but not with lacunes or cerebral microbleeds. Mediation analyses similarly showed that the association between ASC and VCI subgroups may be largely explainable by severity of concomitant CeVD, specifically white matter hyperintensities volume. Our findings indicate that elevated serum ASC levels may reflect a state of inflammasome activation in VCI, particularly in individuals with extensive white matter hyperintensities. These results underscore the potential role of dysregulated inflammasome activation not only as a pathogenic factor but also as a potential therapeutic target for VCI.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag068","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:50:24Z","timestamp":1772628624000},"source":"Crossref","is-referenced-by-count":2,"title":["Elevated serum inflammasome adaptor protein ASC is associated with white matter hyperintensities in vascular cognitive impairment"],"prefix":"10.1093","volume":"8","author":[{"given":"Yuek Ling","family":"Chai","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Memory, Aging and Cognition Centre, National University Health System , Singapore 117599 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-5635","authenticated-orcid":false,"given":"Saima","family":"Hilal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Saw Swee Hock School of Public Health, National University of Singapore , Singapore 117549 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera Yuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Gerald Choa Neuroscience Institute, Li Ka Shing Institute of Health Sciences, Lau Tat-Chuen Research Centre of Brain Degenerative Diseases in Chinese, Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong SAR 999077 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent C T","family":"Mok","sequence":"additional","affiliation":[{"name":"Gerald Choa Neuroscience Institute, Li Ka Shing Institute of Health Sciences, Lau Tat-Chuen Research Centre of Brain Degenerative Diseases in Chinese, Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong SAR 999077 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce R","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Memory, Aging and Cognition Centre, National University Health System , Singapore 117599 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Memory, Aging and Cognition Centre, National University Health System , Singapore 117599 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Yeow","family":"Tan","sequence":"additional","affiliation":[{"name":"St Luke\u2019s Hospital , Singapore 659674 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayanaswamy","family":"Venketasubramanian","sequence":"additional","affiliation":[{"name":"Raffles Neuroscience Centre, Raffles Hospital , Singapore 188770 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiruma V","family":"Arumugam","sequence":"additional","affiliation":[{"name":"La Trobe Institute for Molecular Science, Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University , Bundoora , Victoria 3086 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Li-Hsian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Memory, Aging and Cognition Centre, National University Health System , Singapore 117599 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7685-1424","authenticated-orcid":false,"given":"Mitchell K P","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Memory, Aging and Cognition Centre, National University Health System , Singapore 117599 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"2026041703575310000_fcag068-B1","doi-asserted-by":"crossref","first-page":"18003","DOI":"10.1038\/nrdp.2018.3","article-title":"Vascular cognitive impairment","volume":"4","author":"van der Flier","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"11","key":"2026041703575310000_fcag068-B2","doi-asserted-by":"crossref","first-page":"6224","DOI":"10.3390\/ijms23116224","article-title":"Neuroinflammation in vascular cognitive impairment and dementia: Current evidence, advances, and prospects","volume":"23","author":"Tian","year":"2022","journal-title":"Int J Mol 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