Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease

Background and Purpose-Vascular causes of dementia are increasing in importance because of the aging of the population. Biological markers to distinguish patients with vascular dementia (VaD) from Alzheimer disease (AD) would be very useful. Because cerebrovascular disease increases expression of brain matrix metalloproteinases (MMPs) and tissue inhibitors to metalloproteinases (TIMPs), we hypothesized that MMPs would be elevated in the cerebrospinal fluid (CSF) of patients with VaD, but not in patients with AD. Methods-Fifteen patients with VaD were identified, including dementia caused by multiple infarcts and progressive dementia caused by disease of the small cerebral blood vessels. Patients were followed-up for 4 to 10 years to confirm the diagnosis. Thirty patients with AD were also studied. Patients had CSF collected at their initial evaluation. Gelatinase A (MMP-2) and gelatinase B (MMP-9) were quantified by gelatin-substrate zymography, and TIMPs were measured by reverse zymography. Control CSF was obtained from neurologically normal subjects. Results-MMP-9 levels were significantly elevated in the CSF of VaD patients compared either to those with AD (P<0.0001) or to controls. MMP-2, TIMP-1, and TIMP-2 were similar in patient groups and controls. Conclusions-Patients with multiinfarct and small vessel VaD have elevated levels of MMP-9 in the CSF compared with AD and controls. Although CSF MMP-9 increases in other neurological conditions and is not specific for VaD, it could provide an additional biological marker for the separation of patients with VaD and AD.