Related Experiment Video
Updated: Jul 19, 2025
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals
Mari Aksnes1, Elettra Capogna2, Didac Vidal-Piñeiro2
1Department of Geriatric Medicine, University of Oslo, Oslo, Norway.
Abstract:
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-β42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) may influence brain structure changes during normal aging. Elevated MMP-2 and TIMP-123 levels correlate with age-related brain atrophy in cognitively healthy individuals.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in neurodegeneration and Alzheimer's disease (AD).
- Their specific roles in the normal aging brain remain unclear.
- Understanding these roles is crucial for distinguishing normal aging from pathological processes.
Purpose of the Study:
- To investigate the association between cerebrospinal fluid (CSF) levels of specific MMPs and TIMPs and brain structure changes in cognitively unimpaired individuals.
- To determine if baseline levels or longitudinal changes in MMPs/TIMPs predict brain atrophy or changes in AD biomarkers.
Main Methods:
- Linear mixed models were employed to analyze CSF MMP and TIMP levels against brain imaging data (entorhinal cortex thickness, hippocampal volume, lateral ventricle volume).
- CSF levels of MMP-2, MMP-3, MMP-10, a composite TIMP-123, and TIMP-4 were assessed.
- Changes in CSF amyloid-β42 and phosphorylated tau181 were also evaluated.
Main Results:
- Lower baseline MMP-3 levels predicted larger ventricle volumes and greater entorhinal cortex thinning.
- Increasing MMP-2 levels over time were associated with entorhinal thinning, hippocampal atrophy, and ventricular expansion.
- Increasing TIMP-123 levels over time predicted ventricular expansion.
- No MMPs or TIMPs predicted changes in CSF AD biomarkers (amyloid-β42, phosphorylated tau181).
Conclusions:
- MMPs and TIMPs may contribute to age-associated brain atrophy in cognitively unimpaired individuals.
- Longitudinal increases in MMP-2 and TIMP-123 levels are novel predictors of brain atrophy.
- These findings highlight a potential role for MMPs and TIMPs in the structural changes of normal brain aging.
