Publication
Title
Brain serotonergic and noradrenergic deficiencies in behavioral variant frontotemporal dementia compared to early-onset Alzheimers disease
Author
Abstract
Routinely prescribed psychoactive drugs in behavioral variant frontotemporal dementia (FTD) for improvement of (non)cognitive symptoms are primarily based on monoamine replacement or augmentation strategies. These were, however, initially intended to symptomatically treat other degenerative, behavioral, or personality disorders, and thus lack disease specificity. Moreover, current knowledge on brain monoaminergic neurotransmitter deficiencies in this presenile disorder is scarce, particularly with reference to changes in Alzheimers disease (AD). The latter hence favors neurochemical comparison studies in order to elucidate the monoaminergic underpinnings of FTD compared to early-onset AD, which may contribute to better pharmacotherapy. Therefore, frozen brain samples, i.e., Brodmann area (BA) 6/8/9/10/11/12/22/24/46, amygdala, and hippocampus, of 10 neuropathologically confirmed FTD, AD, and control subjects were analyzed by means of reversed-phase high-performance liquid chromatography. Levels of serotonergic, dopaminergic, and noradrenergic compounds were measured. In nine brain areas, serotonin (5-HT) concentrations were significantly increased in FTD compared to AD patients, while 5-hydroxyindoleacetic acid/5-HT ratios were decreased in eight regions, also compared to controls. Furthermore, in all regions, noradrenaline (NA) levels were significantly higher, and 3-methoxy-4-hydroxyphenylglycol/NA ratios were significantly lower in FTD than in AD and controls. Contrarily, significantly higher dopamine (DA) levels and reduced homovanillic acid/DA ratios were only found in BA12 and BA46. Results indicate that FTD is defined by distinct serotonergic and noradrenergic deficiencies. Additional research regarding the interactions between both monoaminergic networks is required. Similarly, clinical trials investigating the effects of 5-HT1A receptor antagonists or NA-modulating agents, such as α1/2/β1-blockers, seem to have a rationale and should be considered.
Language
Dutch, English
Source (journal)
Journal of Alzheimer's disease
Publication
2016
ISSN
1387-2877
Volume/pages
53:3(2016), p. 1079-1096
ISI
000383148100025
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 21.06.2016
Last edited 09.07.2017
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