Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology

Stuart G. Snowden, Amera A. Ebshiana, Abdul Hye, Olga Pletnikova, Richard O'Brien, An Yang, Juan Troncoso, Cristina Legido-Quigley, Madhav Thambisetty

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)35-43
Number of pages9
JournalJournal of Alzheimer's Disease
Volume72
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Brain Diseases
Neurotransmitter Agents
Alzheimer Disease
Pathology
Asymptomatic Diseases
Temporal Lobe
Dopamine
Cholinesterase Inhibitors
Brain
Prefrontal Cortex
Cerebellum
Cognition
Acetylcholine
Disease Progression
Serotonin
Control Groups

Keywords

  • Asymptomatic Alzheimer's disease
  • brain
  • metabolomics
  • neurotransmitters

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Snowden, S. G., Ebshiana, A. A., Hye, A., Pletnikova, O., O'Brien, R., Yang, A., ... Thambisetty, M. (2019). Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology. Journal of Alzheimer's Disease, 72(1), 35-43. https://doi.org/10.3233/JAD-190577

Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology. / Snowden, Stuart G.; Ebshiana, Amera A.; Hye, Abdul; Pletnikova, Olga; O'Brien, Richard; Yang, An; Troncoso, Juan; Legido-Quigley, Cristina; Thambisetty, Madhav.

In: Journal of Alzheimer's Disease, Vol. 72, No. 1, 01.01.2019, p. 35-43.

Research output: Contribution to journalArticle

Snowden, SG, Ebshiana, AA, Hye, A, Pletnikova, O, O'Brien, R, Yang, A, Troncoso, J, Legido-Quigley, C & Thambisetty, M 2019, 'Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology', Journal of Alzheimer's Disease, vol. 72, no. 1, pp. 35-43. https://doi.org/10.3233/JAD-190577
Snowden, Stuart G. ; Ebshiana, Amera A. ; Hye, Abdul ; Pletnikova, Olga ; O'Brien, Richard ; Yang, An ; Troncoso, Juan ; Legido-Quigley, Cristina ; Thambisetty, Madhav. / Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology. In: Journal of Alzheimer's Disease. 2019 ; Vol. 72, No. 1. pp. 35-43.
@article{11d392a0d8a547e782abe6066122ef66,
title = "Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology",
abstract = "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.",
keywords = "Asymptomatic Alzheimer's disease, brain, metabolomics, neurotransmitters",
author = "Snowden, {Stuart G.} and Ebshiana, {Amera A.} and Abdul Hye and Olga Pletnikova and Richard O'Brien and An Yang and Juan Troncoso and Cristina Legido-Quigley and Madhav Thambisetty",
year = "2019",
month = "1",
day = "1",
doi = "10.3233/JAD-190577",
language = "English (US)",
volume = "72",
pages = "35--43",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",

}

TY - JOUR

T1 - Neurotransmitter Imbalance in the Brain and Alzheimer's Disease Pathology

AU - Snowden, Stuart G.

AU - Ebshiana, Amera A.

AU - Hye, Abdul

AU - Pletnikova, Olga

AU - O'Brien, Richard

AU - Yang, An

AU - Troncoso, Juan

AU - Legido-Quigley, Cristina

AU - Thambisetty, Madhav

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Asymptomatic Alzheimer's disease

KW - brain

KW - metabolomics

KW - neurotransmitters

UR - http://www.scopus.com/inward/record.url?scp=85074434288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074434288&partnerID=8YFLogxK

U2 - 10.3233/JAD-190577

DO - 10.3233/JAD-190577

M3 - Article

C2 - 31561368

AN - SCOPUS:85074434288

VL - 72

SP - 35

EP - 43

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -