Brain Serotonergic and Noradrenergic Deficiencies in Behavioral Variant Frontotemporal Dementia Compared to Early-Onset Alzheimer's Disease

Yannick Vermeiren, Jana Janssens, Tony Aerts, Jean-Jacques Martin, Anne Sieben, Debby Van Dam, Peter P. De Deyn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

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 Alzheimer's 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 alpha(1/2)/beta(1)-blockers, seem to have a rationale and should be considered.

Original languageEnglish
Pages (from-to)1079-1096
Number of pages18
JournalJournal of Alzheimer’s Disease
Volume53
Issue number3
DOIs
Publication statusPublished - 2016

Keywords

  • Alzheimer's disease
  • brain tissue
  • frontotemporal dementia
  • monoamines
  • neurochemistry
  • neuropsychiatric symptoms
  • noradrenaline
  • prefrontal cortex
  • RP-HPLC-ECD
  • serotonin
  • LOBAR DEGENERATION
  • NEUROPSYCHIATRIC SYMPTOMS
  • NEUROTRANSMITTER ALTERATIONS
  • AFFERENT REGULATION
  • NATIONAL INSTITUTE
  • PICKS-DISEASE
  • LEWY BODIES
  • SYSTEM
  • POSTMORTEM
  • ANTAGONIST

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