In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease. (14th April 2020)

• Record Type: Journal Article
• Authors: Terada, Tatsuhiro; Obi, Tomokazu; Bunai, Tomoyasu; Matsudaira, Takashi; Yoshikawa, Etsuji; Ando, Ichiro; Futatsubashi, Masami; Tsukada, Hideo; Ouchi, Yasuomi
• Is Part Of: Neurology. Volume 94:Number 15(2020)
• Publication Date: 2020-04-14
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000009249
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: In vivo glycolysis-related glucose metabolism and electron transport chain-related mitochondrial activity may be different regionally in the brains of patients with Alzheimer disease (AD). To test this hypothesis regarding AD pathophysiology, we measured the availability of mitochondrial complex-I (MC-I) with the novel PET probe [ 18 F]2-tert- butyl-4-chloro-5–2H- pyridazin-3-one ([ 18 F]BCPP-EF), which binds to MC-I, and compared [ 18 F]BCPP-EF uptake with 18 F-fluorodeoxyglucose ([ 18 F]FDG) uptake in the living AD brain. Methods: First, the total distribution volume (VT ) of [ 18 F]BCPP-EF from 10 normal controls (NCs) was quantified using arterial blood samples and then tested to observe whether VT could substitute for the standard uptake value relative to the global count (SUVRg). Eighteen NCs and 14 different NCs underwent PET with [ 18 F]BCPP-EF or [ 18 F]FDG, respectively. Second, 32 patients with AD were scanned semiquantitatively with double PET tracers. Interparticipant and intraparticipant comparisons of the levels of MC-I activity ([ 18 F]BCPP-EF) and glucose metabolism ([ 18 F]FDG) were performed. Results: The [ 18 F]BCPP-EF VT was positively correlated with the [ 18 F]BCPP-EF SUVRg, indicating that the use of the SUVRg was sufficient for semiquantitative evaluation. The [ 18 F]BCPP-EF SUVRg, but not the [ 18 F]FDG SUVRg, was significantly lower in the parahippocampus in patients with AD, highlighting the prominence of oxidative metabolic failure in the medial temporal cortex. Robust positive correlations between the [ 18 F]BCPP-EF SUVRg and [ 18 F]FDG SUVRg were observed in several brain regions, except the parahippocampus, in early-stage AD. Conclusions: Mitochondrial dysfunction in the parahippocampus was shown in early-stage AD. Mitochondria-related energy failure may precede glycolysis-related hypometabolism in regions with pathologically confirmed early neurodegeneration in AD.