Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Department of Preemptive Medicine for Dementia, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Acta Neurol Scand. 2021 Apr;143(4):450-457. doi: 10.1111/ane.13382. Epub 2020 Dec 11.
To clarify pathomechanisms of cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri).
We collected cerebrospinal fluid (CSF) samples of nine patients with CAA-ri of before (acute CAA-ri group) and after treatment (post-treatment CAA-ri group) and nine patients with CAA (CAA without inflammation group). We examined anti-amyloid β protein (Aβ) antibody titer by ELISA, and measured 27 Cytokines, nine matrix metalloproteinases (MMPs), and four tissue inhibitors of MMPs (TIMPs) by multiplexed fluorescent bead-based immunoassay.
We demonstrated TIMP-2 (median) in CSF of the acute CAA-ri group (30,994.49 pg/ml, p = 0.007) and the post-treatment CAA-ri group (36,430.97 pg/ml, p = 0.001) was significantly elevated compared to that of the CAA without inflammation group (22,013.58 pg/ml). TIMP-1 was also higher in the post-treatment CAA-ri group than that in the CAA without inflammation group (58,167.75 pg/ml vs. 45,770.03 pg/ml, p = 0.005). There was a significant positive correlation between TIMP-1 and anti-Aβ antibodies in CAA-ri (r = 0.900, p = 0.037). Median MMP-2 tended to be higher in the acute and post-treatment CAA-ri groups (10,619.82 pg/ml and 8396.98 pg/ml, respectively) than in the CAA without inflammation group (4436.34 pg/ml). Platelet-derived growth factor (PDGF)-BB levels before treatment were higher than those after treatment (median, 12.66 pg/ml vs. 6.39 pg/ml; p = 0.011) and correlated with the titer of anti-Aβ antibodies (r =0.900, p = 0.037).
Elevated levels of MMP-2, TIMP-1, and TIMP-2 might be related to the development of CAA-ri. Elevation of PDGF-BB could be a useful marker for clinical diagnosis of CAA-ri.
阐明脑淀粉样血管病相关炎症/血管炎（CAA-ri）的发病机制。
我们收集了 9 例 CAA-ri 患者治疗前后（急性 CAA-ri 组和治疗后 CAA-ri 组）和 9 例 CAA 患者（无炎症 CAA 组）的脑脊液（CSF）样本。我们通过 ELISA 检测抗淀粉样β蛋白（Aβ）抗体滴度，并通过多重荧光珠免疫测定法测量 27 种细胞因子、9 种基质金属蛋白酶（MMPs）和 4 种基质金属蛋白酶抑制剂（TIMPs）。
我们发现急性 CAA-ri 组（30994.49 pg/ml，p = 0.007）和治疗后 CAA-ri 组（36430.97 pg/ml，p = 0.001）的 CSF 中 TIMP-2（中位数）明显高于无炎症 CAA 组（22013.58 pg/ml）。治疗后 CAA-ri 组的 TIMP-1 也高于无炎症 CAA 组（58167.75 pg/ml 比 45770.03 pg/ml，p = 0.005）。CAA-ri 患者的 TIMP-1 与抗 Aβ 抗体呈显著正相关（r = 0.900，p = 0.037）。急性和治疗后 CAA-ri 组的 MMP-2 中位数均高于无炎症 CAA 组（分别为 10619.82 pg/ml 和 8396.98 pg/ml）。血小板衍生生长因子（PDGF-BB）治疗前水平高于治疗后水平（中位数，12.66 pg/ml 比 6.39 pg/ml；p = 0.011），与抗 Aβ 抗体滴度相关（r = 0.900，p = 0.037）。
MMP-2、TIMP-1 和 TIMP-2 的升高可能与 CAA-ri 的发生有关。PDGF-BB 的升高可能是 CAA-ri 临床诊断的有用标志物。
