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

- Dysfunction of the serotonergic system in Alzheimer's disease could be related to cognitive impairments.
- 5-HT1A receptors are highly expressed in hippocampus and are involved in memory processes.
- 5-HT1A receptors targeting molecules are currently being tested in AD patients.
- 5-HT1A receptors' expression undergoes particular modifications during prodromal stages of AD.
- Hippocampal 5-HT1A receptors' expression regulation and neuronal hyperactivity occur concomitantly in prodromal stage of AD.
- Is hippocampal 5-HT1A receptor' expression regulation beneficial or deleterious in AD progression?
- In the prodromal stages of AD, should 5-HT1A receptor overexpression be stimulated or limited?

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.