RT Journal Article
SR Electronic
T1 Neurotransmitter imbalance in the brain and Alzheimer’s pathology
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 220699
DO 10.1101/220699
A1 Stuart G. Snowden
A1 Amera A. Ebshiana
A1 Abdul Hye
A1 Olga Pletnikova
A1 Richard O’Brien
A1 An Yang
A1 John Troncoso
A1 Cristina Legido-Quigley
A1 Madhav Thambisetty
YR 2018
UL http://biorxiv.org/content/early/2018/07/15/220699.abstract
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.AbbreviationsAAADaromatic amino acid decarboxylaseADAlzheimer’s diseaseASYMADasymptomatic ADBLSABaltimore longitudinal studying of agingCERADconsortium to establish a registry for Alzheimer’s diseaseDSM-III-Rdiagnostic and statistical manual of mental disordersGABAgamma-aminobutyrateITGinferior temporal gyrusL-DOPA’L-dihydroxyphenylalanineMFGmiddle frontal gyrusNINCDS-ADRDAnational institute of neurological and communicative disorders and stroke – Alzheimer’s disease and related disorders associationNMDAN-methyl-D-aspartateTHtyrosine hydrolaseTMtryptophan monooxygenase