Effect of matrix metalloproteinases on the longitudinal change in Alzheimer’s disease (AD) pathology and cognitive function in patients with mild cognitive impairment due to AD

Background Matrix metalloproteinases (MMPs), endopeptidases expressed in brain and immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD). However, the longitudinal effect of MMPs on AD patients is still unclear. Method We used the data of the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4‐positive patients with mild cognitive impairment (MCI) due to AD confirmed with low Aβ42 and/or high phosphorylated‐tau (p‐tau) in cerebrospinal fluid (CSF). We obtained baseline demographic data and plasma MMP levels including MMP‐1, MMP‐2, MMP‐7, MMP‐9, and MMP‐10, and longitudinal data of Aβ42, total tau, and p‐tau in CSF, MRI‐measured hippocampal volume, and cognitive function evaluated on Mini‐Mental State Examination (MMSE) and AD Assessment Scale‐11 (ADAS‐11) over 4 years. We investigated the effect of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampus volume and cognitive function. Result There was no significant association between the baseline MMP levels and the longitudinal change in CSF biomarkers. Baseline MMP‐9 level was associated with a longitudinal decrease of hippocampal volume and deterioration of MMSE and ADAS‐11 scores. Conclusion High plasma MMP‐9 level in the patients with MCI due to AD would be a risk of consequent neurodegeneration and cognitive decline.