Author:
Snowden Stuart G.,Ebshiana Amera A.,Hye Abdul,Pletnikova Olga,O’Brien Richard,Yang An,Troncoso John,Legido-Quigley Cristina,Thambisetty Madhav
Abstract
ABSTRACTINTRODUCTIONThree 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.METHODSTissue 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.RESULTS11 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.DISCUSSIONThese 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.
Publisher
Cold Spring Harbor Laboratory
Reference48 articles.
1. Alzheimer’s Disease International. World Alzheimer’s report 2015, the global impact of dementia: an analysis of prevalence, incidence, cost and trends. 2015.
2. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis;Canadian Medical Association Journal,2003
3. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials
4. Alzheimer's Disease: A Disorder of Cortical Cholinergic Innervation
5. The cholinergic hypothesis of Alzheimer's disease: a review of progress