Background: White matter lesions are frequently found in mild cognitive impairments and Alzheimer’s disease. Matrix metalloproteinases and the tissue inhibitor of metalloproteinases are implicated in amyloid-β catabolism and blood brain barrier permeability. However, it remains unclear whether they are associated with white matter lesions in Alzheimer’s disease.

Objective: The aim of this study was to examine the association of matrix metalloproteinases and tissue inhibitor of metalloproteinases with white matter degeneration in subjects with amyloid-positive mild cognitive impairment.

Methods: Thirty subjects with amnestic mild cognitive impairment (14 men and 16 women; mean age, 75.6 ± 5.8 years) underwent magnetic resonance imaging, 11C-Pittsburgh Compound B positron emission tomography, and 18F-fluorodeoxyglucose positron emission tomography. Levels of plasma matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured using multiplex assays. All subjects had an abnormal brain amyloid burden. Subjects were divided into two groups according to the presence of white matter lesions using the Fazekas scale. Cognitive function testing results i.e., mean 11C-Pittsburgh Compound B and 18F-fluorodeoxyglucose uptake, concentrations of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and matrix metalloproteinases/tissue inhibitor of metalloproteinases ratios were compared between the groups. Correlation analysis was conducted to investigate the association between Fazekas scale score and clinical and neuroimaging variables as well as concentrations of matrix metalloproteinases and tissue inhibitor of metalloproteinases.

Results: Matrix metalloproteinases-2, -8, and -9 levels, matrix metalloproteinases-2/ tissue inhibitor of metalloproteinases-2, matrix metalloproteinases-8/ tissue inhibitor of metalloproteinases-1, and matrix metalloproteinases-9/tissue inhibitor of metalloproteinases-1 significantly increased and tissue inhibitor of metalloproteinases-1 and-2 levels significantly decreased in the group with white matter lesions compared with the group without white matter lesions. Matrix metalloproteinases-2, -8, and -9 levels correlated positively and tissue inhibitor of metalloproteinases-1 and -2 levels correlated negatively with Fazekas scale score.

Conclusion: Plasma matrix metalloproteinases-2, -8, -9 and tissue inhibitor of metalloproteinases-1 and -2 levels are associated with white matter lesions in the mild cognitive impairment stage of Alzheimer’s disease.

背景：白质病变常见于轻度认知障碍和阿尔茨海默病。基质金属蛋白酶和金属蛋白酶的组织抑制剂与淀粉样蛋白-β 分解代谢和血脑屏障通透性有关。然而，尚不清楚它们是否与阿尔茨海默病的白质病变有关。

目的：本研究的目的是检查基质金属蛋白酶和金属蛋白酶组织抑制剂与淀粉样蛋白阳性轻度认知障碍受试者白质变性的关联。

方法：30 名患有遗忘型轻度认知障碍的受试者（14 名男性和 16 名女性；平均年龄，75.6 ± 5.8 岁）接受了磁共振成像、11C-匹兹堡化合物 B 正电子发射断层扫描和 18F-氟脱氧葡萄糖正电子发射断层扫描。血浆基质金属蛋白酶和金属蛋白酶组织抑制剂的水平使用多重测定法测量。所有受试者都有异常的脑淀粉样蛋白负荷。使用 Fazekas 量表根据白质病变的存在将受试者分为两组。认知功能测试结果，即平均 11C-匹兹堡化合物 B 和 18F-氟脱氧葡萄糖摄取、基质金属蛋白酶和金属蛋白酶组织抑制剂的浓度，以及基质金属蛋白酶/金属蛋白酶组织抑制剂的比率在组之间进行比较。

结果：基质金属蛋白酶-2、-8和-9水平，基质金属蛋白酶-2/金属蛋白酶组织抑制剂-2、基质金属蛋白酶-8/金属蛋白酶组织抑制剂-1和基质金属蛋白酶-9/金属蛋白酶组织抑制剂-与无白质病变组相比，有白质病变组的金属蛋白酶1和金属蛋白酶组织抑制剂-1和-2水平显着降低。基质金属蛋白酶-2、-8 和 -9 水平与 Fazekas 量表评分呈正相关，金属蛋白酶组织抑制剂-1 和 -2 水平呈负相关。

结论：血浆基质金属蛋白酶-2、-8、-9和金属蛋白酶组织抑制剂-1和-2水平与阿尔茨海默病轻度认知障碍阶段的白质病变有关。