Hippocampal 5-HT1A receptor expression changes in prodromal stages of Alzheimer's disease: Beneficial or deleterious?

There is increasing evidence that the serotonergic system is highly dysfunctional in Alzheimer's disease (AD), and this could be related to cognitive impairments associated with dementia. Of the various serotonin receptors, 5-HT1A receptors are relevant to AD as they are highly expressed in the human hippocampus and are known to be involved in the regulation of memory processes. This review will discuss the involvement of 5-HT1A receptors in AD at several levels (post-mortem, in-vivo imaging, animal models). The involvement of this receptor subtype in AD pathophysiology will be reviewed particularly in terms of the modulation of its expression in the hippocampal region. Hypotheses involving 5-HT1A receptors will be developed, from two points of view: 5-HT1A receptors expression regulation as being beneficial and needing to be pharmacologically stimulated; and 5-HT1A receptors expression modulation as deleterious and needing to be limited. Finally, we will propose perspectives for future experiments that should weigh in favor of one or the other of the two hypotheses.