Neurotransmitter imbalance in the brain and alzheimer’s pathology

Stuart G. Snowden; Amera A. Ebshiana; Abdul Hye; Olga Pletnikova; Richard O’Brien; An Yang; John Troncoso; Cristina Legido-Quigley; Madhav Thambisetty

doi:10.1101/220699

Neurotransmitter imbalance in the brain and alzheimer’s pathology

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

INTRODUCTION: Three of the four treatments for Alzheimer’s disease are cholinesterase inhibitors targeting the pathological reduction of acetylcholine levels. Here we aimed to determine the role of other neurotransmitter pathways in AD pathology. METHODS: Tissue samples were obtained from three groups, controls, AD and ‘asymptomatic AD’ 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: 11 of 15 measured metabolites were shown to be associated with disease. Decreases in dopamine were seen in the ASYMAD group in the MFG when compared to control and AD patients (FC=0.78, p=4.1×10-3). In AD patients changes were mainly seen in the ITG’s inhibitory GABAergic system. DISCUSSION: These results indicate that dopamine could be depleted in brains with Alzheimer’s pathology but intact cognition, while and imbalance of several neurotransmitters is evident in the brain of AD patients.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/220699
State	Published - Nov 17 2017

Keywords

Alzheimer’s disease
Asymptomatic AD
Brain
Metabolomics
Neurotransmitters

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1101/220699

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title = "Neurotransmitter imbalance in the brain and alzheimer{\textquoteright}s pathology",

abstract = "INTRODUCTION: Three of the four treatments for Alzheimer{\textquoteright}s disease are cholinesterase inhibitors targeting the pathological reduction of acetylcholine levels. Here we aimed to determine the role of other neurotransmitter pathways in AD pathology. METHODS: Tissue samples were obtained from three groups, controls, AD and {\textquoteleft}asymptomatic AD{\textquoteright} 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: 11 of 15 measured metabolites were shown to be associated with disease. Decreases in dopamine were seen in the ASYMAD group in the MFG when compared to control and AD patients (FC=0.78, p=4.1×10-3). In AD patients changes were mainly seen in the ITG{\textquoteright}s inhibitory GABAergic system. DISCUSSION: These results indicate that dopamine could be depleted in brains with Alzheimer{\textquoteright}s pathology but intact cognition, while and imbalance of several neurotransmitters is evident in the brain of AD patients.",

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author = "Snowden, {Stuart G.} and Ebshiana, {Amera A.} and Abdul Hye and Olga Pletnikova and Richard O{\textquoteright}Brien and An Yang and John Troncoso and Cristina Legido-Quigley and Madhav Thambisetty",

note = "Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2017",

month = nov,

day = "17",

doi = "10.1101/220699",

language = "English (US)",

journal = "Unknown Journal",

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T1 - Neurotransmitter imbalance in the brain and alzheimer’s pathology

AU - Snowden, Stuart G.

AU - Ebshiana, Amera A.

AU - Hye, Abdul

AU - Pletnikova, Olga

AU - O’Brien, Richard

AU - Yang, An

AU - Troncoso, John

AU - Legido-Quigley, Cristina

AU - Thambisetty, Madhav

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2017/11/17

Y1 - 2017/11/17

N2 - INTRODUCTION: Three of the four treatments for Alzheimer’s disease are cholinesterase inhibitors targeting the pathological reduction of acetylcholine levels. Here we aimed to determine the role of other neurotransmitter pathways in AD pathology. METHODS: Tissue samples were obtained from three groups, controls, AD and ‘asymptomatic AD’ 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: 11 of 15 measured metabolites were shown to be associated with disease. Decreases in dopamine were seen in the ASYMAD group in the MFG when compared to control and AD patients (FC=0.78, p=4.1×10-3). In AD patients changes were mainly seen in the ITG’s inhibitory GABAergic system. DISCUSSION: These results indicate that dopamine could be depleted in brains with Alzheimer’s pathology but intact cognition, while and imbalance of several neurotransmitters is evident in the brain of AD patients.

AB - INTRODUCTION: Three of the four treatments for Alzheimer’s disease are cholinesterase inhibitors targeting the pathological reduction of acetylcholine levels. Here we aimed to determine the role of other neurotransmitter pathways in AD pathology. METHODS: Tissue samples were obtained from three groups, controls, AD and ‘asymptomatic AD’ 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: 11 of 15 measured metabolites were shown to be associated with disease. Decreases in dopamine were seen in the ASYMAD group in the MFG when compared to control and AD patients (FC=0.78, p=4.1×10-3). In AD patients changes were mainly seen in the ITG’s inhibitory GABAergic system. DISCUSSION: These results indicate that dopamine could be depleted in brains with Alzheimer’s pathology but intact cognition, while and imbalance of several neurotransmitters is evident in the brain of AD patients.

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Neurotransmitter imbalance in the brain and alzheimer’s pathology

Abstract

Keywords

ASJC Scopus subject areas

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