• Soichiro Kitamura, Hitoshi Shimada, Fumitoshi Niwa, Hironobu Endo, Hitoshi Shinotoh, Keisuke Takahata, Manabu Kubota, Yuhei Takado, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, and Makoto Higuchi.
• Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
• J. Neurol. Neurosurg. Psychiatr. 2018 Nov 1; 89 (11): 120812141208-1214.

ObjectiveApathy is a common neuropsychological symptom in Alzheimer's disease (AD), and previous studies demonstrated that neuronal loss and network disruption in some brain regions play pivotal roles in the pathogenesis of apathy. However, contributions of tau and amyloid-β (Aβ) depositions, pathological hallmarks of AD, to the manifestation of apathy remain elusive.MethodsSeventeen patients with AD underwent positron emission tomography (PET) with 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and 11C-Pittsburgh compound-B (11C-PiB) to estimate tau and Aβ accumulations using standardised uptake value ratio (SUVR) images. 11C-PBB3 and 11C-PiB SUVR were compared between AD patients with high and low Apathy Scale (AS) scores. Additionally, volumetric and diffusion tensor MRI was performed in those areas where any significant difference was observed in PET analyses. Correlation and path analyses among AS and estimated imaging parameters were also conducted.ResultsAD patients with high AS scores showed higher 11C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while 11C-PiB SUVR in any brain regions did not differ between them. Elevated 11C-PBB3 SUVR in OFC, decreased OFC thickness and decreased fractional anisotropy (FA) in the uncinate fasciculus (UNC), which is structurally connected to OFC, correlated significantly with increased scores of the AS. Path analysis indicated that increased 11C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC.ConclusionsThe present findings suggested that tau pathology in OFC may provoke focal neurotoxicity in OFC and the following disruption of the OFC-UNC network, leading to the emergence and progression of apathy in AD.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

28 keywords...

hide…