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Tau-induced focal neurotoxicity and network disruption related to apathy in Alzheimer’s disease
OBJECTIVE: Apathy 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, path...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6227800/ https://www.ncbi.nlm.nih.gov/pubmed/29884723 http://dx.doi.org/10.1136/jnnp-2018-317970 |
Sumario: | OBJECTIVE: Apathy 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. METHODS: Seventeen patients with AD underwent positron emission tomography (PET) with (11)C-pyridinyl-butadienyl-benzothiazole 3 ((11)C-PBB3) and (11)C-Pittsburgh compound-B ((11)C-PiB) to estimate tau and Aβ accumulations using standardised uptake value ratio (SUVR) images. (11)C-PBB3 and (11)C-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. RESULTS: AD patients with high AS scores showed higher (11)C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while (11)C-PiB SUVR in any brain regions did not differ between them. Elevated (11)C-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 (11)C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC. CONCLUSIONS: The 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. |
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