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PET imaging for the characterization of tauopathies : Alzheimer's disease and chronic traumatic encephalopathy

Abstract : Tauopathies are neurodegenerative diseases characterized by intracerebral aggregation of abnormal Tau proteins. During this university thesis, we studied by Positon Emission Tomography (PET) imaging the Tau burden in Alzheimer’s Disease (AD) and Chronic Traumatic Encephalopathy (CTE), two different taupotahies with similar Tau isoforms. In this context, our first objective was to determine the ability of Tau PET imaging to improve the diagnosis of AD and to determine the viability of a new potential treatment. We have established that Tau PET imaging was able to detect the beneficial effect of a non-invasive brain stimulation, called transcranial alternating current stimulation (tACS) in people with AD. Our second objective was to determine the usefulness of Tau PET imaging in vivo in a population of American football players to help the early detection of CTE. We have demonstrated that in our population, Tau PET imaging was able to highlight the Tau pathology in early stages of CTE. In parallel, we have studied by autoradiography post-mortem from patients with neuro-pathological diagnosis of AD and CTE the binding pattern of three radiotracers widely used in research for Tau imaging. We directly compared the binding properties of [18F]-AV-1451 with [18F]-MK-6240 and [18F]-PI-2620 in the same specimens. These three tracers showed similar strong binding pattern to Tau protein in AD and a lack of binding in CTE brain slices. In total, these experiments allow to confirm the potential utility of Tau PET tracers for the reliable detection, quantification of Tau aggregates and disease-progression tracking in AD, while it remains questionable for CTE.
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Submitted on : Thursday, October 15, 2020 - 2:59:12 PM
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Maëva Dhaynaut. PET imaging for the characterization of tauopathies : Alzheimer's disease and chronic traumatic encephalopathy. Medical Imaging. Sorbonne Université, 2019. English. ⟨NNT : 2019SORUS197⟩. ⟨tel-02968207⟩

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