Plasma energy substrates at two stages of Alzheimer’s disease in humans

In Alzheimer’s disease (AD), the presence of amyloid-β peptide may impair cell energy formation by altering both anaerobic and aerobic metabolism. This study aimed to estimate possible alterations in circulating energy substrates. In 54 community-dwelling AD subjects, fasting peripheral venous blood samples were drawn in the morning to determine the energy substrates lactate, pyruvate and ketone bodies (KBs, β-hydroxybutyrate and acetoacetate). Plasma lactate levels in the entire AD population were significantly lower than in healthy controls (P < 0.01), whereas pyruvate concentrations were similar. This is particularly evident in AD subjects with diagnosis time >5 years. Moreover, both plasma lactate and pyruvate were lower in subjects with AD >5 years than in subjects with AD ⩽5 years (P < 0.001 for lactate; P = 0.04 for pyruvate). KB concentrations were normal in both subgroups. Lactate was inversely related to diagnosis time (r = −0.42; P = 0.002). In conclusion, subjects with AD, particularly those with a longer diagnosis time, show considerable reductions in circulating lactate and pyruvate as an expression of altered muscular metabolic pathways that generate energy.