Objectives: In animal models and in vitro studies leptomeninges have been shown to be the origin of neurotrophic substances that support the survival and growth of neuronal cells. Because dementia is associated with neuronal loss, we investigated whether leptomeningeal dysfunction may be involved in the pathogenesis of dementia disorders. Methods: We analysed the cerebrospinal fluid (CSF) concentrations of the leptomeningeal derived b trace protein, b2 microglobulin, and cystatin C.Results: There was a statistically significant difference of the CSF b trace protein levels among different groups. Patients with idiopathic normal pressure hydrocephalus (NPH) (17.5 (SD 4.3) mg/l) showed significantly lower CSF b trace protein levels than patients with Alzheimer's disease (23.8 (6.2) mg/l), depression (24.2 (7.3) mg/l), and normal controls (25.3 (4.9) mg/l). To patients with vascular dementia (20.1 (5.6) mg/l) and frontotemporal dementia (21.9 (7.0) mg/l), the difference was not significant. There was no significant difference regarding the CSF and serum concentrations of b2 microglobulin or cystatin C among the different groups. Conclusions:We conclude that leptomeningeal dysfunction may be involved in certain types of dementia such as NPH and that reduced CSF b trace protein levels in patients with NPH may aid in differentiating this difficult to diagnose disorder from other syndromes such as Alzheimer's disease. T he leptomeninges have been shown to support the survival and growth of neuronal cells and to produce neurotrophic factors. [1][2][3][4] Because dementia is associated with neuronal loss, leptomeningeal dysfunction may be a possible pathomechanism in dementia syndromes. In Alzheimer's disease, the leptomeninges have been shown to be a major site of b amyloid deposition. 5 In idiopathic normal pressure hydocepalus (NPH), several studies showed a leptomeningeal fibrosis of unknown origin.6 7 To assess meningeal function in vivo, we measured cerebrospinal fluid (CSF) proteins produced by the leptomeninges. b Trace protein has been shown to be mainly synthesised in the spinal leptomeninges and pachymeninx.8 9 It seems to have a function related to prostaglandin metabolism 10 and to act as a carrier protein for retinoids.11 b2 microglobulin is a cell membrane associated peptide expressed on the surface of most nucleated cells that may be involved in immunological reactions.12 Cystatin C is an important extracellular inhibitor of cysteine proteinases. 13The aim of this study was to investigate concentrations of CSF proteins with a known leptomeningeal origin in various subtypes of dementia to determine whether signs of meningeal dysfunction are present. METHODSPaired lumbar CSF and serum samples were obtained from 96 patients from the department of neurology, University Hospital of Ulm, with different subtypes of dementia.We examined 30 patients (18 female, 12 male) fulfilling the diagnostic criteria of Alzheimer's disease as described by McKhann et al.14 Furthermore, we investigated 13 patients (6 female, 7 ma...