Preservation of cortical histamine H-3 receptors in ischemic vascular and mixed dementias

Abstract

Aim: Histamine H3 receptor antagonists have been proposed as a novel therapeutic approach for the symptomatic treatment of Alzheimer's disease (AD). However, it is unclear whether there is a neurochemical basis for extending their potential use in vascular and mixed dementias. In this study, we measured cortical H3 receptors in patients with subcortical ischemic vascular dementia (SIVD) and mixed SIVD/AD (MIX). Materials and methods: Radioligand binding assays using [3H]GSK189254 were used to measure H3 receptors in the postmortem frontal cortex, anterior cingulate gyrus and hippocampus of a cohort of longitudinally assessed SIVD, MIX and age-matched controls. Results: H3 receptor levels were unchanged in SIVD and MIX in all areas studied. Furthermore, frontal H3 receptor densities negatively correlated with predeath assessment of cognition using Mini-Mental State Examination (MMSE) scores. Conclusion: Our data suggest that H3 receptors are preserved in SIVD and MIX, thus supporting further assessments of H3 antagonists as potential therapeutics in these dementias. © 2011 Elsevier B.V. All rights reserved.