[p2–095]: analysis of neurodegenerative disease‐related pathology in the retina and olfactory bulb of rodent models

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Major hallmarks of the disease are extracellular plaque deposits of the β-amyloid peptide (Aβ) and formation of intracellular neurofibrillary tangles, composed of tau protein in the brain tissue. Previous studies have reported the implication of functional impairments of the sensory systems in AD. In fact, retinal structural deficits and visual dysfunctions are often experienced by AD patients providing an opportunity to track this disease in the retina. This study aims to analyze the neuropathological changes occurring both in brain and retina of different AD animal models and address suitable biomarkers for early screening tests for AD. Eyes and brains from various AD animal models (APP rat, TAU rat, TMHT mouse) aged 6 and 12 months are collected. Right eyes and hemibrains are cryosectioned for immunohistochemical labelling, while left eyes and hemibrains are frozen for further biochemical and molecular characterization. For immunohistochemical analysis, a range of antibodies have been employed to detect and quantitatively analyze different neuropathological markers present in retina, primary and secondary visual cortex (visual system), as well as in the olfactory bulb and piriform cortex (olfactory system). AD rodent models show a significant age-dependent shift in neuropathology-related biomarkers when compared to controls, although the results might vary due to the existing biological differences between mice and rats, and retina and brain tissue. In all sections, an overall increase in Aβ and tau protein is expected (Amyloid, Tau). Additional analyses will focus on different neurotransmitters (chAT, GAD67, TH), neuronal cells, glial cells and synapses (NeuN, GFAP, F4/80, PSD95, Piccolo). Our results will strengthen the hypothesis that AD manifests in eyes, particularly the retina, and provide evidence for the possibility to track the disease utilizing the appropriate AD biomarkers.