Immunocytochemical study of the dorsal and median raphe nuclei in patients with Alzheimer's disease prospectively assessed for behavioural changes.

The dorsal and median raphe nuclei were examined with immunocytochemistry to display the 5-HT neurones in 16 cases of post-mortem-proven Alzheimer's disease (AD) and 12 age and sex-matched controls. The AD cases had been prospectively assessed during life for expression of behavioural changes as well as for cognitive decline. A significant (P < 0.001) 41% reduction in density of dorsal raphe neurones was found along with a significant (P < 0.02) 29% reduction in density of median raphe neurones in AD. There were significantly more neurofibrillary tangles in both dorsal and median raphe nuclei in AD than in controls (P < 0.001). There was no correlation between reduction in neurone density in these nuclei and behavioural change, cognitive decline, neurofibrillary tangle counts in these nuclei or plaque and tangle pathology in frontal and temporal cortex. It was concluded from these findings that the raphe nuclei are significantly affected by the pathology of AD and that plasticity in the 5-HT system is the probable reason for the lack of correlation of reduced 5-HT neurone density and clinical disease parameters.