TAU PHOSPHORYLATION AFTER HEAVY ALCOHOL CONSUMPTION DURING ADOLESCENCE IN P301S MICE

The intake of ethanol, among other neurotoxic compounds, results in brain alterations such as inflammation and gliosis which also occur during the development of Alzheimer’s disease (AD). AD is characterized by the accumulation of β-amyloid and the phosphorylation of tau protein in the hippocampus and neocortex. Although the relationship between alcohol consumption and AD has been proposed, the impact that this type of intake during critical neurodevelopmental periods, like adolescence, on the onset of AD remains largely unknown. Here we examined whether heavy alcohol consumption during adolescence might affect tau phosphorylation in P301S mice, an AD murine model. We performed an adolescent intermittent alcohol treatment paradigm (PROEX 199.1/23) in P301S and wild type mice, by intragastric administration of either water or ethanol (5 g/kg – 25% EtOH, w/v), throughout their adolescence (P25-P55). Mice were then left unperturbed until P200, when they were sacrificed and their brains extracted and sectioned. Sections were processed by immunofluorescence with antibodies that recognize Ser202/Thr205 (AT8 antibodies) and Thr231 (p231 antibodies) tau phosphorilation sites. Using fluorescence microscopy we found no clear alterations in transgenic mice with heavy alcohol consumption in the density of AT8 positive neurons nor in the intensity of p231 immunostaining. The results suggest that alcohol consumption during adolescence seems not to contribute to the pathological Tau phosphorylation in AD disease, at least in the early stages. We are currently studying, in the APP-PS1 mouse model of amyloidosis, whether ethanol consumption affects the appearance of β-amyloid plaques, the other major histopathological alteration of AD.