Change in Expression of 5-HT 6 Receptor at Different Stages of Alzheimer’s Disease: A Postmortem Study with the PET Radiopharmaceutical [ 18 F]2FNQ1P

Abstract

Background:

The 5-HT₆ receptor is one of the most recently identified serotonin receptors in the central nervous system. Because of its role in memory and cognitive process, this receptor might be implicated in Alzheimer’s disease (AD) and associated disorders.

Objective:

The aim of this study was to investigate the binding of [¹⁸F]2FNQ1P, a new specific radiotracer of 5-HT₆ receptors, and to quantify 5-HT₆ receptor density in caudate nucleus in a population of patients with different AD stages.

Methods:

Patients were classified according to the “ABC” NIA-AA classification. In vitro binding assays were performed in postmortem brain tissue from the healthy control (HC; n = 8) and severe AD (“High”; n = 8) groups. In vitro quantitative autoradiography was performed in human brain tissue (caudate nucleus) from patients with different stages of AD: HC (n = 15), “Low” (n = 18), “Int” (n = 20), and “High” (n = 15).

Results:

In vitro binding assays did not show significant differences for the K_D and B_max parameters between “High” and HC groups. In vitro quantitative autoradiography showed a significant difference between the “High” and HC groups (p = 0.0025). We also showed a progressive diminution in [¹⁸F]2FNQ1P specific binding, which parallels 5-HT₆ receptors expression, according to increasing AD stage. Significant differences were observed between the HC group and all AD stages combined (“Low”, “Intermediate”, and “High”) (p = 0.011).

Conclusion:

This study confirms the interest of investigating the role of 5-HT₆ receptors in AD and related disorders. [¹⁸F]2FNQ1P demonstrated specific binding to 5-HT₆ receptors.