OBJECTIVE The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aβ42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aβ42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.

中文翻译：

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血浆基质金属蛋白酶水平对阿尔茨海默病神经影像学倡议数据库中注册的 AD 导致的轻度认知障碍患者的阿尔茨海默病 (AD) 生物标志物和认知功能的纵向变化的影响

目的 本研究调查了血浆基质金属蛋白酶 (MMPs) 对阿尔茨海默病 (AD) 相关生物标志物在脑脊液 (CSF)、脑萎缩和 AD 所致轻度认知障碍 (MCI) 患者认知功能纵向变化的影响。 -广告）。方法 我们使用来自阿尔茨海默病神经影像学倡议数据库的数据。我们纳入了 95 名 ApoE4 阳性的 MCI-AD 患者，他们被证实在 CSF 中具有低 Aβ42 和/或高磷酸化 tau (p-tau)。我们获得了基线人口统计学数据、血浆 MMP 水平，包括 MMP-1、-2、-7、-9、-10 和 MMP-1 的组织抑制剂 (TIMP-1)，Aβ42、总 tau 和CSF 中的 p-tau，MRI 测量的海马体积，4 年内通过简易精神状态检查 (MMSE) 和 AD 评估量表-11 (ADAS-11) 评估的认知功能。我们使用线性混合回归分析检查了基线 MMP 水平对 CSF AD 生物标志物、海马体积和认知功能的纵向变化的影响。结果 MCI-AD 患者和对照组之间的基线血浆 MMP 水平没有显着差异，除了 MMP-10，MCI-AD 中 MMP-10 显着低于对照组。MMPs 的基线水平与脑脊液生物标志物的纵向变化无关。MMSE 和 ADAS-11 评估的海马体积和认知功能的下降在 MMP-9 基线水平高的 MCI-AD 患者中明显快于基线 MMP-9 水平处于中低水平的患者。