ELUCIDATING THE COMBINED EFFECTS OF AMYLOID AND TAU IN A NOVEL BIGENIC RAT MODEL WITH HUMAN ALZHEIMER’S DISEASE‐LIKE PATHOLOGY

Background Both amyloid beta (Aβ) and tau pathologies co-exist in Alzheimer’s disease. While studies have shown that Aβ interaction results elevated AD pathology, it is not clearly understood how they might affect one another during early pathology stages leading to plaque formation. This study aimed at determining which extent a combination of gradually developing exacerbate each other the context disease-like novel transgenic rat model. Methods Heterozygous McGill-R-Thy1-APP R955-hTau single rats were crossed, producing bigenic model with both human pathologies, named McGill-R-APPxhTau955. Bigenic express APP Swedish Indiana mutations (KM670/671NL, V717F) as well longest isoform (2N4R) P301S mutation causative frontotemporal dementia. Transgenic (n = 10-12) raised cohorts 12, 20 24 months age subject battery behavioural testing for cognition. Examination inflammatory neurodegenerative processes, was performed primarily using immunohistochemistry (IHC) Western blot (WB). Levels amyloid, p-tau measured CSF, brain blood serum by electrochemiluminescence immunoassays. animals compared transgenics wild-type littermate controls. Results APPxR955-hTau produced gradual accumulation tau, resulting progressive cognitive deficits Alzheimer-like pathology. We discovered compensatory effect on cognition long-term potentiation months, rescuing amyloid-induced effects. However, age, displayed worsened spatial learning memory. Reflective these findings, developed an increased phosphorylaton Status biomarker levels, neuroinflammation neurodegeneration are actively under investigation expected trend similarly. Conclusions The McGill-R-APPxhTau rat, slow progressing attractive further mechanisms proteins another, observation changes elucidation disease stages.