Regulation of neurotransmitter synthesis in Alzheimer's disease - Potential for novel disease biomarkers

Introduction: There currently is an unmet need for new diagnostics to monitor Alzheimer’s disease (AD) and a lack of understanding of the metabolic processes, in particular leucine deprivation on disease and the autophagy pathway. It is thought that there is an altered metabolic profile related to AD that could be used to monitor the progression of patients and offer possible targets for treatment. Findings: The results presented show for the first time that measurement of BCATm and the amino acids increased the sensitivity and specificity of MoCA analysis in correctly identifying participants free of AD pathology (100%) but also those with the disease to 90% accuracy, with BCATm and Glutamate, significantly improve the predictive potential of MoCA, and significantly improve the predictive potential of the MRI measures. Additionally, this research has shown that leucine and nutrient deprivation causes a significant decrease in intracellular glutamic acid and causes increased expression of markers of autophagy Beclin 1 and LC3. Metabolic analysis has additionally shown that in cases of acute leucine deprivation cellular metabolism is significantly altered.