Early intervention with ABA prevents neuroinflammation and memory impairment in a triple transgenic mice model of Alzheimer´s disease

Neuroinflammation and insulin resistance in the brain are intimately linked to neurodegenerative disorders, including Alzheimer’s disease. Even though traditionally Alzheimer´s disease has been associated to Aβ deposits and hyperphosphorylated Tau intracellular tangles, several studies show that neuroinflammation may be the initial cause that triggers degeneration. Accordingly, a number of natural supplements that improves brain insulin sensitivity and reduce neuroinflammation have been proposed as good choices in the therapeutic prevention of cognitive decline. Further supporting this evidence, we show that phytohormone Abscisic Acid, can prevent memory impairment and neuroinflammation markers in a triple transgenic mouse model, where no peripheral inflammatory changes have occurred. Moreover, our data strongly suggests that early intervention is critical for good prognosis, and that cognitive improvement requires longer treatment than recovering neuroinflammation markers

The Neurovascular Unit Dysfunction in Alzheimer's Disease

Funding: This work was supported by Fondo Nacional de Ciencia y Tecnologia (FONDOCyT) from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to M.P.-H.) and (2018-2019-2A3-208 to J.L.-M. and M.P.-H.). Acknowledgments: The authors want to express their gratitude to the Mexican families who have donated the brain of their loved ones affected by Alzheimer’s disease and made our research possible. We also want to express our gratitude to the Union Medical University Clinic, Dominican Republic, for their support and collaboration in developing of this research project. This work is dedicated to the memory of José Raúl Mena López †.Peer reviewedPublisher PD

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Funding: This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to J.L.-M. and M.P.-H). Acknowledgments: The authors want to express their gratitude to the following: P. Davies†(Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder† (North Western, Chicago, IL, USA) for the generous gift of mAbs TG-3 and Alz-50, and Tau-1, Tau-5, and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medica University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected by Alzheimer’s disease and made our research possible. This work is dedicated to the memory of José Raúl Mena López† . †Deceased.Peer reviewedPublisher PD

PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer’s Disease

FUNDING This work was supported by Fondo Nacional de Ciencia, Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015- 3A2-127 to MP-H and 2018-2019-2A3-208 to JL-M and MP-H). ACKNOWLEDGMENTS: We want to express our gratitude to the following: Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, United States) and Lester I. Binder† (North Western, Chicago, IL, United States) for the generous gifts of mAbs TG3 and Alz-50, and Tau-1, Tau-5, and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; Samadhi Moreno-Campuzano for her technical assistance/support in the confocal microscopy unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medical University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer’s disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López† .Peer reviewedPublisher PD

Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection

Acknowledgements We want to express our gratitude to the Union Medical University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer's disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López†.Peer reviewedPublisher PD

Tau Protein Phosphorylated at Threonine-231 Is Expressed Abundantly in the Cerebellum in Prion Encephalopathies

ACKNOWLEDGMENTS: The authors want to express their gratitude to the following: Dr. P. Davies † (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder † (North Western, Chicago, IL, USA) for the generous gift of mAbs TG-3 and Alz-50, and Tau-1, Tau-5 and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medica University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer's disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López †. †Deceased. This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to JL-M and MP-H).Peer reviewedPublisher PD

Molecular Processing of Tau Protein in Progressive Supranuclear Palsy : Neuronal and Glial Degeneration

ACKNOWLEDGMENTS This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to JL-M and MP-H). The authors want to express their gratitude to the following: Dr. P. Davies† (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder† (North Western, Chicago, IL, USA) for the generous gift of mAbs TG–3 and Alz–50, and Tau–1, Tau–5 and Tau–7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politecnico Nacional; Union Medica Uni- A. Mart´ınez-Maldonado et al. / Molecular Processing of Tau Protein in Progressive Supranuclear Palsy 1529 versity Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer’s disease and made our research possible. This work is dedicated to the memory of Professor Dr. Jose Ra ´ ul Mena L ´ opez ´ †. †Deceased. Authors’ disclosures available online (https:// www.j-alz.com/manuscript-disclosures/20-1139r2).Peer reviewedPublisher PD

Rapid β-amyloid deposition and cognitive impairment after cholinergic denervation in APP/PS1 mice

Although extensive evidence supports the role of amyloid-β (Aβ) in Alzheimer disease (AD), the neurotoxic mechanisms underlying AD pathogenesis are not understood. On the other hand, neuronal loss is the pathological feature that best correlates with cognitive impairment. We hypothesized that cholinergic neurodegeneration may lead to Aβ deposition and tested this by inducing selective cholinergic lesions in APPswe/PS1dE9 mice with murine p75(NTR) saporin (mu p75-SAP). Intracerebroventricular lesions that removed ~50% of cholinergic innervation to the cortex and hippocampus were induced in animals with incipient (~3 months) and marked (~7 months of age) Aβ deposition. Cranial windows were implanted and Aβ deposition was monitored in vivo using multiphoton microscopy. Aβ deposition was increased as soon as 7 days after the lesion and this effect was maintained up to 3 months later. Postmortem studies using immunohistochemistry with an anti-Aβ antibody corroborated these findings in both cerebral cortex and hippocampus. Tau phosphorylation was also significantly increased after the lesions. Cholinergic denervation resulted in early memory impairment at 3 months of age that worsened with age (~7 months); there was a synergistic effect between cholinergic denervation and the presence of APP/PS1 transgenes. Altogether, our data suggest that cholinergic denervation may trigger Aβ deposition and synergistically contribute to cognitive impairment in AD patients

Un modelo de aprendizaje colaborativo para la Edad Moderna: el recurso a las TICs y su aplicación a un entorno de docencia virtual

Depto. de Dibujo y GrabadoFac. de Bellas ArtesFALSEsubmitte

Un modelo de aprendizaje colaborativo para la Edad Moderna: el recurso a las TICS y su aplicación a un entorno de docencia virtual II

Depto. de Historia Moderna y ContemporáneaFac. de Geografía e HistoriaFALSEsubmitte