HUMAN AD AND MOUSE MODELS: PE3-ABETA AND TAU–ASSOCIATED PATHOLOGY

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles. Neuritic plaques often appear in N-terminally truncated forms with a cyclic glutamate residue. pE3 Aβ exhibits cellular toxicity, presents a high self-aggregation predisposition and promotes co-aggregation of non-modified Aβ. The current study is designed to analyze features of AD-related pathological changes in human brain that are spatially associated with pE-Aβ immunoreactive structures, and to verify whether similar changes are present in different animal models of AD. Human paraffin slides of AD patients as well as healthy controls and, cryosections of transgenic mouse models (5xFAD, APPSL) and non-transgenic control mice were labelled by multichannel immunofluorescence to analyze the spatial relations of pE3 Aβ and tau. Therefore, a rabbit polyclonal antibody against pE3 Aβ and a mouse monoclonal antibody (clone AT8) against pSer202/Thr205 tau were used. All samples were digitised and the assessment of immunofluorescent labelling was performed quantitatively by image analysis. Depending on genotype and age, mouse models manifest different expressions of pE3 Aβ and tau. 5xFAD mice show a significantly increased pE3 Aβ and tau expression over age, while APPSL mice only show a significant increase of pE3 Aβ at the age of 12 months. Furthermore, expression of pE3 Aβ and tau significantly correlated in both mouse models. Human AD cases showed an increasing pE3 Aβ expression with progressing Braak stages. Expression of tau is only increased in patients of Braak stage V/VI. Additionally, a significant correlation between pE3 Aβ and tau expression in human sections could be observed. Correlation between pE3 Aβ and tau expression in human samples as well as in mouse model samples confirms an interdependent expression of pE3 Aβ and tau. Further studies will be required to investigate how these proteins affect each other.