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Neurotransmitter Imbalance in the Brain and Alzheimer’s Disease Pathology

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  • Stuart G Snowden
  • Amera Ebshiana
  • Abdul Hye
  • Olga Pletnikova
  • Richard O'Brien
  • Yang An
  • Juan C. Troncoso
  • Cristina Legido-Quigley
  • Madhav Thambisetty
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BACKGROUND: Cholinesterase inhibitors represent three of the four treatments for Alzheimer's disease (AD), and target the pathological reduction of acetylcholine levels. Here we aimed to study the role of other neurotransmitter pathways in AD pathology.

OBJECTIVE: This study aimed to determine associations between AD pathology at both symptomatic and asymptomatic stages of disease progression, and the metabolism of a range of non-cholinergic neurotransmitters.

METHODS: Tissue samples were obtained from three groups, controls, AD, and 'asymptomatic AD' (ASYMAD), i.e., cognitively normal individuals that had significant AD neuropathology. Three brain areas were studied, the middle frontal gyrus (MFG), the inferior temporal gyrus (ITG), and the cerebellum.

RESULTS: 12 of 15 metabolites involved in neurotransmitter metabolism were shown to be associated with AD pathology. Decreases in dopamine were most pronounced in the MFG with lower levels seen in the ASYMAD group compared to control (FC = 0.78, p = 2.9×10-2). In the ITG significant changes were seen in GABAergic and serotonin metabolism between control and AD patients; however, these changes were not seen between control and ASYMAD individuals.

CONCLUSION: These results indicate that dopamine could be depleted in brains with AD pathology but intact cognition, while an imbalance of several neurotransmitters is evident in the brains of AD patients.
Original languageEnglish
JournalJournal of Alzheimer's Disease
Volume72
Issue number1
Pages (from-to)35-43
Number of pages8
ISSN1387-2877
Publication statusPublished - 29 Oct 2019
Externally publishedYes

ID: 58576713