Disruption of mitochondrial respiration and the monoamine neurotransmitter system in Alzheimer's disease

Abstract Alzheimer's disease (AD) is associated with mitochondrial dysfunction and disturbances in neurotransmitter systems. Depression is a common comorbidity of AD, and the disruption of monoaminergic neurotransmission may be involved in the pathophysiology of AD. Assessment of mitochondrial dysfunction was performed by measuring mitochondrial respiratory rate; changes in monoamine neurotransmission were evaluated by measuring mitochondrial monoamine oxidase B (MAO-B) activity and serotonin transporter (SERT) activity in platelets. The decreases in the maximum capacity of the electron transport system and a decrease in the respiratory reserve capacity compared to controls was significant in intact platelets of AD patients but not in vascular dementia (VD) patients, indicating some specificity of these biomarkers for AD. In permeabilized platelets, parameters of mitochondrial respiration were not significantly altered in AD, suggesting that the reduction observed in intact platelets may be due to impaired availability of respiratory chain enzyme substrates. MAO-B activity and SERT activity were not significantly different between controls and AD and VD patients. The association of biochemical parameters with cognitive decline and comorbid depression in subjects with AD and VD showed the applicability of mitochondrial respiration in intact platelets, but not MAO-B activity and SERT activity, as a blood biomarker of AD.