Matrix Metalloproteinase-Mediated Neuroinflammation in Vascular Cognitive Impairment of the Binswanger Type

Vascular cognitive impairment (VCI) is a heterogeneous group of diseases linked together by cerebrovascular disease. Treatment of VCI has been hindered by the lack of a coherent pathophysiological process that could provide molecular targets. Of the several forms of VCI, the small vessel disease form is both the most prevalent and generally has a progressive course. Binswanger's disease (BD) is the small vessel form of VCI that involves extensive injury to the deep white matter. Growing evidence suggests that there is disruption of the blood-brain barrier (BBB) secondary to an inflammatory state. Matrix metalloproteinases (MMPs) are increased in the brain and CSF of patients with BD, and have been shown to disrupt the BBB in animal studies, suggesting that they may be biomarkers and therapeutic targets. Multimodal biomarkers derived from clinical, neuropsychological, imaging, and biochemical data can be used to narrow the VCI population to the progressive inflammatory form that will be optimal for treatment trials. This review describes the role of the MMPs in pathophysiology and their use as biomarkers.