Meningeal derived cerebrospinal fluid proteins in different forms of dementia: is a meningopathy involved in normal pressure hydrocephalus?

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 beta trace protein, beta2 microglobulin, and cystatin C.

RESULTS: There was a statistically significant difference of the CSF beta trace protein levels among different groups. Patients with idiopathic normal pressure hydrocephalus (NPH) (17.5 (SD 4.3) mg/l) showed significantly lower CSF beta 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 beta2 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 beta trace protein levels in patients with NPH may aid in differentiating this difficult to diagnose disorder from other syndromes such as Alzheimer's disease.