Department of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Alzheimers Res Ther. 2023 Jan 30;15(1):26. doi: 10.1186/s13195-023-01171-3.
To evaluate the potential of cerebrospinal fluid (CSF) levels of matrix metalloproteinases and tissue-type inhibitors (MMP; TIMP), and ratios of MMPs to TIMPs, to function as biomarkers for sporadic or hereditary cerebral amyloid angiopathy (CAA).
CSF concentrations of the matrix metalloproteinases MMP-2, MMP-9 and MMP-14, as well as the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, were determined using immunoassays. These assays were applied to two, independent study groups of sporadic CAA (sCAA) (n = 28/43) and control subjects (n = 40/40), as well as to groups of pre-symptomatic (n = 11) and symptomatic hereditary Dutch-CAA (D-CAA) patients (n = 12), and age-matched controls (n = 22/28, respectively).
In the sCAA/control cohorts, inconsistent differences were found for individual MMPs and TIMPs, but MMP-2/TIMP-2 (discovery/validation: p = 0.004; p = 0.02) and MMP-14/TIMP-2 ratios (discovery/validation: p < 0.001; p = 0.04) were consistently decreased in sCAA, compared to controls. Moreover, MMP-14 was decreased in symptomatic D-CAA (p = 0.03), compared to controls. The MMP-14/TIMP-1 (p = 0.03) and MMP-14/TIMP-2 (p = 0.04) ratios were decreased in symptomatic D-CAA compared to controls and also compared to pre-symptomatic D-CAA (p = 0.004; p = 0.005, respectively).
CSF MMP-2/TIMP-2 and MMP-14/TIMP-2 were consistently decreased in sCAA, compared to controls. Additionally, MMP-14/TIMP-2 levels were also decreased in symptomatic D-CAA, compared to both pre-symptomatic D-CAA and controls, and can therefore be considered a biomarker for sporadic and late-stage hereditary forms of CAA.
评估脑脊液（CSF）中基质金属蛋白酶和组织抑制剂（MMP；TIMP）的水平，以及 MMP 与 TIMP 的比值，作为散发性或遗传性脑淀粉样血管病（CAA）的生物标志物的潜力。
使用免疫测定法测定基质金属蛋白酶 MMP-2、MMP-9 和 MMP-14 以及组织抑制剂金属蛋白酶 TIMP-1、TIMP-2 和 TIMP-3 的 CSF 浓度。这些测定方法应用于两个独立的散发性 CAA（sCAA）研究组（n=28/43）和对照组（n=40/40），以及无症状（n=11）和有症状的遗传性荷兰-CAA（D-CAA）患者组（n=12），以及年龄匹配的对照组（分别为 n=22/28）。
在 sCAA/对照组队列中，个别 MMP 和 TIMP 存在不一致的差异，但 MMP-2/TIMP-2（发现/验证：p=0.004；p=0.02）和 MMP-14/TIMP-2 比值（发现/验证：p<0.001；p=0.04）在 sCAA 中均低于对照组。此外，与对照组相比，症状性 D-CAA 患者的 MMP-14 水平降低（p=0.03）。与对照组相比，症状性 D-CAA 患者的 MMP-14/TIMP-1（p=0.03）和 MMP-14/TIMP-2（p=0.04）比值降低，与无症状性 D-CAA 相比（p=0.004；p=0.005）。
与对照组相比，sCAA 中 CSF MMP-2/TIMP-2 和 MMP-14/TIMP-2 均降低。此外，与无症状性 D-CAA 相比，症状性 D-CAA 患者的 MMP-14/TIMP-2 水平也降低，与无症状性 D-CAA 和对照组相比，因此可以作为散发性和晚期遗传性 CAA 的生物标志物。
