Carmen Infante-Garcia, Spain
University of Cadiz Division of PhysiologyAuthor Of 1 Presentation
LIRAGLUTIDE REDUCES AMILOID PATHOLOGY AND MICROGLIA ACTIVATION IN A MIXED MURINE MODEL OF ALZHEIMER´S DISEASE AND TYPE 2 DIABETES
Abstract
Aims
Objectives: We analyzed the long-term liraglutide (LRGT) as an alternative treatment to retard or slow down metabolic, amyloid-β (Aβ) and inflammatory pathologies in a mixed model of AD and T2D (APP/PS1xdb/db mouse).
Methods
Methods: AD-T2D mice were produced by cross-breeding APPswe/PS1dE9 with db/db mice. We administered LRGT to these mice (500μg/kg/day, sc) for 20 weeks. Body weight, glucose and insulin levels were evaluated before treatment and every 4 weeks until sacrifice. Amyloid pathology was studied and senile plaques (SP) were analyzed by immunohistochemistry with 4G8 antibody and thioflavin-S staining. Soluble and insoluble Aβ40 and Aβ42 levels, as well as Aβ oligomers were determined by ELISA. The inflammatory pathology was analyzed by immunostaining for microglia with Iba-1 antibody, in the proximity and far from SP.
Results
Results: LRGT treatment maintains insulin levels and decreases glucose levels in the long term. Interestingly, LRGT reduces Aβ pathology and SP burden is reduced in APP/PS1 and SP size is reduced in APP/PS1 and APP/PS1xdb/db mice in the cortex. Moreover, it is also disclosed that LRGT treatment lessens oligomeric Aβ in the cortex from APP/PS1xdb/db mice. Likewise, LRGT treatment reduces cortical microglia burden in the proximity of SP from AD mice, whereas microglia burden is reduced in SP free areas from diabetic mice.
Conclusions
Conclusions: LRGT treatment limits metabolic compromise in diabetic mice. LRGT reduces oligomeric Aβ levels and the treatment limits microglia activation in APP/PS1xdb/db mice, supporting that LRGT might be as an alternative to slow down amyloid and inflammatory pathologies associated with AD and T2D.