Matrix-metalloproteinases are associated with white matter damage in older adults


Introduction: Matrix metalloproteinases (MMPs) regulate extracellular matrix remodeling and blood-brain barrier permeability, but associations with white matter integrity are unknown. This study relates cerebrospinal fluid (CSF) biomarkers of MMP-2, MMP-3, and MMP-9 to white matter integrity.

Methods: Participants underwent lumbar puncture and brain MRI. Linear regressions and voxel-wise analyses related biomarkers to white matter macrostructure and microstructure.

Results: Lower MMP-2 and higher MMP-3 were associated with compromised white matter microstructure (p-values<0.05). Diagnosis, APOE-ε4, and Aβ modified associations, with higher MMP levels relating to compromised white matter microstructure among normal cognition, APOE-ε4 non-carriers, and Aβ negative groups. Associations were reversed among mild cognitive impairment, APOE-ε4 carriers, and Aβ positive groups.

Discussion: MMPs may represent one pathway to white matter injury in aging, but among individuals at risk for Alzheimer’s disease, MMPs may be protective. In conjunction with other biomarkers, MMPs may provide valuable information about white matter health in older adults.

Submitted to Alzheimer’s and Dementia