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
N1 - Publisher Copyright:
© 2019 - IOS Press and the authors. All rights reserved.
PY - 2019
Y1 - 2019
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
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U2 - 10.3233/JAD-190577
DO - 10.3233/JAD-190577
M3 - Article
C2 - 31561368
AN - SCOPUS:85074434288
SN - 1387-2877
VL - 72
SP - 35
EP - 43
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -