Plasma amyloid beta levels and platelet mitochondrial respiration in patients with Alzheimer's disease
Abstrakt
Objectives: Altered amyloid metabolism and mitochondrial dysfunction play key roles in the development of Alzheimer's disease (AD). We asked whether an association exists between disturbed platelet mitochondrial respiration and the plasma concentrations of A beta(40) and A beta(42) in patients with AD.
Design and methods: Plasma A beta(40) and A beta(42) concentrations and mitochondrial respiration in intact and permeabilized platelets were measured in 50 patients with AD, 15 patients with vascular dementia and 25 control subjects. A pilot longitudinal study was performed to monitor the progression of AD in a subgroup 11 patients with AD.
Results: The mean A beta(40), A beta(42) and A beta(42)/A beta(40) levels were not significantly altered in patients with AD compared with controls. The mitochondrial respiratory rate in intact platelets was significantly reduced in patients with AD compared to controls, particularly the basal respiratory rate, maximum respiratory capacity, and respiratory reserve; however, the flux control ratio for basal respiration was increased.
A correlation between the plasma A beta(42) concentration and mitochondrial respiration in both intact and permeabilized platelets differs in controls and patients with AD. Conclusions: Based on our data, (1) mitochondrial respiration in intact platelets, but not the A beta level itself, may be included in a panel of biomarkers for AD; (2) dysfunctional mitochondrial respiration in platelets is not explained by changes in plasma A beta concentrations; and (3) the association between mitochondrial respiration in platelets and plasma A beta levels differs in patients with AD and controls.
The results supported the hypothesis that mitochondrial dysfunction is the primary factor contributing to the development of AD.