Browsing by Keyword "Alzheimer"
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Item MRI Deep Learning-Based Solution for Alzheimer’s Disease Prediction(2021-09-09) Saratxaga, Cristina L.; Moya, Iratxe; Picón, Artzai; Acosta, Marina; Moreno-Fernandez-de-Leceta, Aitor; Garrote, Estibaliz; Bereciartua-Perez, Arantza; VISUAL; COMPUTER_VISION; QuantumBackground: Alzheimer’s is a degenerative dementing disorder that starts with a mild memory impairment and progresses to a total loss of mental and physical faculties. The sooner the diagnosis is made, the better for the patient, as preventive actions and treatment can be started. Al though tests such as the Mini-Mental State Tests Examination are usually used for early identification, diagnosis relies on magnetic resonance imaging (MRI) brain analysis. Methods: Public initiatives such as the OASIS (Open Access Series of Imaging Studies) collection provide neuroimaging datasets openly available for research purposes. In this work, a new method based on deep learning and image processing techniques for MRI-based Alzheimer’s diagnosis is proposed and compared with previous literature works. Results: Our method achieves a balance accuracy (BAC) up to 0.93 for image-based automated diagnosis of the disease, and a BAC of 0.88 for the establishment of the disease stage (healthy tissue, very mild and severe stage). Conclusions: Results obtained surpassed the state-of-the-art proposals using the OASIS collection. This demonstrates that deep learning-based strategies are an effective tool for building a robust solution for Alzheimer’s-assisted diagnosis based on MRI data.Item Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies(Taylor and Francis Ltd., 2022) Akwa, Yvette; Di Malta, Chiara; Zallo, Fátima; Gondard, Elise; Lunati, Adele; Diaz-de-Grenu, Lara Z.; Zampelli, Angela; Boiret, Anne; Santamaria, Sara; Martinez-Preciado, Maialen; Cortese, Katia; Kordower, Jeffrey H.; Matute, Carlos; Lozano, Andres M.; Capetillo-Zarate, Estibaliz; Vaccari, Thomas; Settembre, Carmine; Baulieu, Etienne E.; Tampellini, DavideSynapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and psychiatric disorders, produced positive effects in AD patients. However, the molecular mechanisms underlying the protective role(s) of brain stimulation are still elusive. We have previously demonstrated that induction of synaptic activity exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing the macroautophagy/autophagy flux and lysosomal degradation of pathological MAPT/Tau. We now provide evidence that TFEB (transcription factor EB), a master regulator of lysosomal biogenesis and autophagy, is a key mediator of this cellular response. In cultured primary neurons from FTD-transgenic mice, synaptic stimulation inhibits MTORC1 signaling, thus promoting nuclear translocation of TFEB, which, in turn, induces clearance of MAPT/Tau oligomers. Conversely, synaptic activation fails to promote clearance of toxic MAPT/Tau in neurons expressing constitutively active RRAG GTPases, which sequester TFEB in the cytosol, or upon TFEB depletion. Activation of TFEB is also confirmed in vivo in DBS-stimulated AD mice. We also demonstrate that DBS reduces pathological MAPT/Tau and promotes neuroprotection in Parkinson disease patients with tauopathy. Altogether our findings indicate that stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau. This mechanism, underlying the protective effect of DBS, provides encouraging support for the use of synaptic stimulation as a therapeutic treatment against tauopathies.