RT Journal Article T1 Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer's Disease and Type 2 Diabetes. A1 Infante-Garcia, Carmen A1 Ramos-Rodriguez, Juan Jose A1 Hierro-Bujalance, Carmen A1 Ortegon, Esperanza A1 Pickett, Eleanor A1 Jackson, Rosemary A1 Hernandez-Pacho, Fernando A1 Spires-Jones, Tara A1 Garcia-Alloza, Monica K1 Alzheimer’s disease K1 Amyloid-beta K1 Hemorrhage K1 Inflammation K1 Polypill K1 Tau K1 Type 2 diabetes AB Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor. In order to test the effects of PP at the central level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db mouse. We have analyzed AD pathological features and the underlying specific characteristics that relate AD and T2D. As expected, metabolic alterations were ameliorated after PP treatment in diabetic mice, supporting a role for PP in maintaining pancreatic activity. At central level, PP reduced T2D-associated brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid pathologies were also reduced after PP treatment. Furthermore, we observed a reduction of spontaneous central bleeding and inflammation after PP treatment in diabetic mice. As consequence, learning and memory processes were improved after PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further analyze the role of PP, as an alternative or adjuvant, to slow down or delay the central complications associated with T2D and AD. YR 2017 FD 2017-12-09 LK http://hdl.handle.net/10668/11891 UL http://hdl.handle.net/10668/11891 LA en DS RISalud RD Feb 16, 2025