Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease
Tatsuhiro Terada, Joseph Therriault, Min Su Kang, Mélissa Savard, Tharick A. Pascoal, Firoza Z Lussier, Cécile Tissot, Yi-Ting Wang, Andréa Lessa Benedet, Takashi Matsudaira, Tomoyasu Bunai, Tomokazu Obi, Hideo Tsukada, Yasuomi Ouchi, Pedro Rosa‐Neto
Abstract
Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [ 18 F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [ 18 F]BCPP-EF mitochondrial function, [ 11 C]PBB3 for tau deposition, and [ 11 C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [ 18 F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [ 11 C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [ 18 F]BCPP-EF SUVR and [ 11 C]PBB3 BP ND (R = 0.2679, p = 0.04), but not [ 11 C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [ 11 C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.