Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia
Matthew P. Pase, Jayandra J. Himali, Raquel Puerta, Alexa Beiser, Mitzi M. Gonzales, Claudia L. Satizábal, Qiong Yang, Hugo J. Aparicio, Daniel Kojis, Charles DeCarli, Oscar L. López, W.T. Longstreth, Vilmundur Guðnason, Thomas H. Mosley, Joshua C. Bis, Alison E. Fohner, Bruce M. Psaty, Merçé Boada, Pablo García‐González, Sergi Valero, Marta Marquié, Russell P. Tracy, Lenore J. Launer, Agustı́n Ruiz, Myriam Fornage, Sudha Seshadri
Abstract
BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. RESULTS: = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. DISCUSSION: Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.