血浆 YKL-40 与 MRI、CSF 以及脑健康和痴呆认知标志物的关联。

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

机构信息

From the Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Australia; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (J.J.H., M.M.G.), University of Texas Health Sciences Center, San Antonio; ACE Alzheimer Center (R.P., M.B., P.G.-G., S.V., M.M., A.R.), Barcelona, Spain; Boston University School of Public Health (A.S.B., D.J.K.), MA; University of Texas Health Sciences Center (C.L.S., S.S.), San Antonio; Department of Neurology (Q.Y., H.J.A.), Boston University School of Medicine, MA; Department of Neurology (C.S.D.), School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California at Davis; Department of Neurology (O.L.L.), School of Medicine, University of Pittsburgh, PA; University of Washington (W.L., B.M.P.), Seattle; Faculty of Medicine (V.G.), University of Iceland, Reykjavík; University of Mississippi Medical Center (T.H.M.), The MIND Center, Jackson; Cardiovascular Health Research Unit (J.C.B.), Department of Medicine, and Department of Epidemiology (A.F.), University of Washington, Seattle; University of Vermont (R.T.), Burlington; Laboratory of Epidemiology and Population Sciences (L.J.L.), National Institute on Aging, NIH, Bethesda, MD; and University of Texas Health Science Center (M.F.), Houston. Matthew P. Pase is currently at the School of Psychological Sciences and the Turner Institute for Brain and Mental Health, Monash University, Australia.

出版信息

Neurology. 2024 Feb 27;102(4):e208075. doi: 10.1212/WNL.0000000000208075. Epub 2024 Jan 30.

DOI:10.1212/WNL.0000000000208075

PMID:38290090

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11383876/

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

Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated ( = 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.

摘要

背景与目的

脑脊液中较高的 YKL-40 水平是大脑炎症的已知生物标志物。我们探索了血浆 YKL-40 作为加速大脑老化和痴呆风险的生物标志物的效用。

方法

我们在美国或欧洲的 4 个基于社区的队列中进行了横断面和前瞻性分析：年龄、基因/环境易感性-雷克雅未克研究、社区动脉粥样硬化风险研究、年轻人冠状动脉风险发展研究和弗雷明汉心脏研究（FHS）。使用 Mesoscale Discovery 从储存的血浆中测量 YKL-40，每个队列内对水平进行对数转换和标准化。结果包括 MRI 总脑体积、海马体积和作为颅内体积百分比的白质高信号体积（WMHV）、神经心理学测试得出的一般认知综合评分（SD 单位 [SDU]）以及痴呆的发病风险。我们试图在基于临床的 ACE csf 队列中复制与痴呆的关联，该队列也从 CSF 中测量了 YKL-40。

结果

MRI 结果的荟萃分析包括 6558 名无痴呆参与者，用于认知分析的参与者为 6670 名。血液采集与 MRI/认知评估之间的时间最长可达 10.6 年。平均年龄范围从 50 岁到 76 岁，男性占 39%-48%。在研究估计的随机效应荟萃分析中，YKL-40 水平的每 SDU 增加与总脑体积减小相关（β=-0.33；95%CI-0.45 至-0.22；<0.0001）和认知能力下降（β=-0.04；95%CI-0.07 至-0.02；<0.01），经过人口统计学变量调整后。YKL-40 水平与海马体积或 WMHV 无关。在 FHS 中，YKL-40 水平的每 SDU 增加与随后中位 5.8 年的随访中痴呆发病风险增加 64%相关，经过人口统计学变量调整后（风险比 1.64；95%CI 1.25-2.16；<0.001）。在 ACE csf 队列中，血浆和 CSF YKL-40 相关（=0.31），并且两者都与从轻度认知障碍到痴呆的转化相关，独立于淀粉样蛋白、tau 和神经退行性变状态。