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Authors & Affiliations
Georg Ladurner, Daurer Magdalena, Roland Rabl, Stefanie Flunkert, Livia Breznik, Bernhard Baumann, Manuela Prokesch
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, characterized by the appearance of amyloid-beta plaques and neurofibrillary tangles leading to the loss of neurons, cognitive impairments, and death. With 55 million affected people worldwide as of 2019 and an increasing prevalence in an aging society, AD poses a serious challenge for health care systems. Lacking reliable and non-invasive methods of early diagnosis, analyzing the early disease development is of utmost importance for the development of presymptomatic diagnostic tools and treatment options. Diabetes is one of the strongest risk factors for AD, sharing a disturbed insulin signaling pathway, defective protein processing and inflammation with the neurodegenerative disease. The present study aims at investigating the connection between AD and diabetes. Therefore, high fat diet in combination with streptozotocin injections on 5 consecutive days was used to induce diabetes in C57BL/6 mice. Strongly elevated fasting glucose levels indicated a successful disease development. Subsequently, cognitive abilities as well as visual capabilities of animals were analyzed by behavioral testing and the retinal disease pathology was analyzed by immunofluorescence. No signs of visual impairment were found in behavioral tests. The Morris water maze showed less hippocampus-dependent search strategies in treated animals. Complete analysis of histological data will reveal if retinal amyloid pathology is already visible at the stage of diabetes present in the study. Additionally, a completely new behavioral test is currently under development to access different types of memory to allow a more diverse examination of memory deficits in cognitively impaired mice.