A Novel Mouse Model of Alzheimer’s Disease Exhibits Pathology through Synergistic Interactions of Amyloid-β, Tau, and Reactive Astrogliosis

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features, including amyloid-β plaques, neurofibrillary tangles, and reactive astrogliosis. Developing effective diagnostic, preventative, and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease. Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD. Additionally, these models are limited in their ability to elucidate the interplay among amyloid-β plaques, neurofibrillary tangles, and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation. In this study, we introduce a novel AD mouse model (APP/PS1-TauP301L-Adeno mice) designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms. Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAV