Aging-related tau astrogliopathy (ARTAG) is defined by the presence of two types of tau-bearing astrocytes: thorn-shaped astrocytes (TSAs) and granular/fuzzy astrocytes in the brain of old-aged individuals. The present study is focused on TSAs in rare forms of ARTAG with no neuronal tau pathology or restricted to entorhinal and transentorhinal cortices, to avoid bias from associated tauopathies. TSAs show 4Rtau phosphorylation at several specific sites and abnormal tau conformation, but they lack ubiquitin and they are not immunostained with tau-C3 antibodies which recognize truncated tau at Asp421. Astrocytes in ARTAG have atrophic processes, reduced glial fibrillary acidic protein (GFAP) and increased superoxide dismutase 2 (SOD2) immunoreactivity. Gel electrophoresis and western blotting of sarkosyl-insoluble fractions reveal a pattern of phospho-tau in ARTAG characterized by two bands of 68 and 64 kDa, and several middle bands between 35 and 50 kDa which differ from what is seen in AD. Phosphoproteomics of dissected vulnerable regions identifies an increase of phosphorylation marks in a large number of proteins in ARTAG compared with controls. GFAP, aquaporin 4, several serine-threonine kinases, microtubule associated proteins and other neuronal proteins are among the differentially phosphorylated proteins in ARTAG thus suggesting a hyper-phosphorylation background that affects several molecules, including many kinases and proteins from several cell compartments and various cell types. Finally, present results show for the first time that tau seeding is produced in neurons of the hippocampal complex, astrocytes, oligodendroglia and along fibers of the corpus callosum, fimbria and fornix following inoculation into the hippocampus of wild type mice of sarkosyl-insoluble fractions enriched in hyper-phosphorylated tau from selected ARTAG cases. These findings show astrocytes as crucial players of tau seeding in tauopathies.

Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer’s disease (AD) and sporadic Parkinson’s disease (sPD). Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2, Pick’s disease (PiD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD-tau). The studies have disclosed variable gene regulation which is: (1) disease-dependent in the frontal cortex area 8 in AD, sPD, sCJD MM1 and VV2, PiD, PSP and FTLD-tau; (2) region-dependent as seen when comparing the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 (FC) in AD; the substantia nigra, putamen, FC, and angular gyrus in PD, as well as the FC and cerebellum in sCJD; (3) genotype-dependent as seen considering sCJD MM1 and VV2; and (4) stage-dependent as seen in AD at different stages of disease progression. These observations show that regulation of inflammation is much more complicated and diverse than currently understood, and that new therapeutic approaches must be designed in order to selectively act on specific targets in particular diseases and at different time points of disease progression.

RESUMENEl presente estudio se diseñó para mejorar el sistema de vigilancia de las enfermedades vesiculares en México, bajo el sistema de planeación estratégica, identificando las zonas endémicas a través de la estabilidad de linajes virales del serotipo Nueva Jersey, y analizando epidemiológicamente la información generada en 32 años de vigilancia e investigación. Se presentan los resultados que permitieron caracterizar epidemiológicam ente las áreas donde se mantiene el virus de estomatitis vesicular de manera secular en México, y con ello, los componentes necesarios para la construcción de la Matriz de Indicadores para Resultados (MIR) para e l programa de vigilancia de las enfermedades vesiculares en México, que pueden también servir para otros países afectados por esta enfermedad. Adicionalmente se aportan elementos para la prevención de la enfermedad, así como mejorar el comercio internacional de animales de países endémicos de estomatitis vesicular. ABSTRACTThe present study aims to improve the surveillance system of vesicular diseases in Mexico, using the strategic planning system, by identifying endemic areas in which the New Jersey serotype viral lineages are stable and by analyzing the information generated during 32 yr of monitoring. The study shows the necessary elements for building the Matrix of Results Indicators (MRI) that could be used on the vesicular diseases surveillance program in Mexico and in other affected countries. The results that allowed the characterization of the epidemiological areas where the virus of vesicular stomatitis (VS) remains in a secular way in Mexico are presented. Elements for disease prevention are also provided in order to improve the live animal international trade.

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