Murine Non-Transgenic Models of Alzheimer's Disease Pathology: Focus on Risk Factors

Alzheimer's disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include Aβ senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize Aβ transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research.