期刊
ALZHEIMERS & DEMENTIA
卷 14, 期 12, 页码 1640-1650出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2018.06.2857
关键词
Neurovascular unit; Mild cognitive impairment; Elderly; CSF; Serum; Biomarkers; sICAM-1; VEGF; IL-8; MDC; Serum amyloid A; IL-16; Cytokines; Chemokines; Angiogenesis; HDL metabolism
资金
- Swiss National Research Foundation [SNF 320030_141179]
- NATIONAL INSTITUTE ON AGING [P30AG008017] Funding Source: NIH RePORTER
Introduction: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. Methods: Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index >9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline. Results: Mean age was 70 years, mean Mini-Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline (P = .015). Cerebrospinal fluid intercellular adhesion molecule-1, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC of 0.92 for BBB impairment. Serum interleukin-16, vascular endothelial growth factor-D, interleukin-15, and other variables generated an area under the curve of 0.92. Discussion: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated. Cell adhesion, neutrophil migration, high-density lipoprotein metabolism, and angiogenesis are implicated. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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