Journal Article

Multireceptor fingerprints in progressive supranuclear palsy

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

2017

Overview

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 (A 1 ) 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 A 1 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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aged / Aged, 80 and over / Alzheimer's disease / Autoradiography / Biomedical and Life Sciences / Biomedicine / Brain research / Caudate nucleus / Caudate Nucleus - metabolism / Caudate Nucleus - pathology / Cohort Studies / Dementia / Disease / Dopamine / Feasibility studies / Female / Frontal presentation / Geriatric Psychiatry / Geriatrics/Gerontology / Gyrus Cinguli - metabolism / Gyrus Cinguli - pathology / Humans / Laboratories / Male / Medical imaging / Medical research / Midcingulate cortex / Middle Aged / Neurology / Neuropathology / Neurosciences / Neurotransmitter receptors / Progressive supranuclear palsy / Receptors, Neurotransmitter - metabolism / Rodents / Severity of Illness Index / Supranuclear Palsy, Progressive - metabolism / Supranuclear Palsy, Progressive - pathology / Synaptic Transmission - physiology / tau Proteins - metabolism