Involvement of the Serotonergic System in Cognitive and Behavioral Symptoms of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a chronic progressive disorder characterized by dementia, but often featuring behavioral and psychological syndromes (BPSD), such as depression, overactivity, psychosis or aggressive behavior. Traditional treatments for BPSD are neuroleptics and sedatives, which are not devoid of serious adverse effects. Neurochemically, the classical hallmark of AD is the disruption of basal forebrain cholinergic pathways and consequent cortical cholinergic denervation of the neocortex and hippocampus. However, it is conceivable that, according to the complexity and diversity of BPSD, more than one transmitter system may contribute to a particular behavioral syndrome. The serotonergic system has been implicated not only in cognitive processes, but also in depression, psychosis or aggression. In AD, extensive serotonergic denervation has been reported. In particular, there is growing interest in the pathological functions and implication in BPSD of 5-HT6 receptors, due to its high affinity for antipsychotic drugs and its distribution in the brain. In this study we will review the present knowledge of the involvement of the serotonergic system and its receptors in cognitive deficits and BPSD. From the currently available data, it is possible to conclude that pharmacological manipulation of serotonergic system may improve not only cognitive function but behavioral disturbances in dementia.