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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Multireceptor fingerprints in progressive supranuclear palsy

Authors: Wang Zheng Chiu, Laura Donker Kaat, Agnita J. W. Boon, Wouter Kamphorst, Axel Schleicher, Karl Zilles, John C. van Swieten, Nicola Palomero-Gallagher

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups.

Methods

In vitro receptor autoradiography was used to quantify densities of 20 different receptors in the caudate nucleus and midcingulate area 24' of patients with PSP (n = 16) and age- and sex-matched control subjects (n = 14).

Results

Densities of γ-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor type 2, and N-methyl-d-aspartate receptors were significantly higher in area 24′ of patients with PSP, where tau impairment was stronger than in the caudate nucleus. Kainate and nicotinic cholinergic receptor densities were significantly lower, and adenosine receptor type 1 (A1) receptors significantly higher, in the caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP subgroups when clinical parameters such as occurrence of frontal presentation and tau pathology severity were taken into consideration.

Conclusions

We demonstrate, for the first time to our knowledge, that kainate and A1 receptors are altered in PSP and that clinically identifiable PSP subgroups differ at the neurochemical level. Numerous receptors were altered in the midcingulate cortex, further suggesting that it may prove to be a key region in PSP. Finally, we add to the evidence that nondopaminergic systems play a role in the pathophysiology of PSP, thus highlighting potential novel treatment strategies.
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Metadata
Title
Multireceptor fingerprints in progressive supranuclear palsy
Authors
Wang Zheng Chiu
Laura Donker Kaat
Agnita J. W. Boon
Wouter Kamphorst
Axel Schleicher
Karl Zilles
John C. van Swieten
Nicola Palomero-Gallagher
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0259-5

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