Intrathecal release of nitric oxide in Alzheimer's disease and vascular dementia

A growing body of evidence points out the potential role of inflammatory me chanisms in the pathophysiology of brain damage in dementia. We have recent ly demonstrated that patients with Alzheimer's disease (AD) and vascular de mentia (VaD) display an intrathecal production of proinflammatory cytokines . TNF-alpha, one of these cytokines, leads to the production of nitric oxid e (NO), a potent inflammatory mediator, by induction of inducible NO syntha se. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO, and to relate its levels to the degree of intellectual impairment, in patients with AD and VaD. Twenty patients with early AD and 26 patients with VaD were analyzed with respect to cerebrospinal fluid levels of nitrate by gas chromatography/mass spectro metry. Interestingly, in patients with AD but not VaD, the intrathecal leve ls of nitrate were significantly and inversely correlated (r = -0.68, p = 0 .002) to the degree of intellectual impairment. Our study demonstrates an i nverse correlation between the intrathecal levels of nitrate and the degree of cognitive impairment in patients with AD, suggesting a neuroprotective effect of NO in AD. Copyright (C) 2000 S. Karger AG, Basel.