In Vivo Seeding of Amyloid-β Protein and Implications in Modeling Alzheimer's Disease Pathology

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing amyloid β-protein (Aβ) and intracellular neurofibrillary tangles formed by tau. Cerebral Aβ accumulation initiates a noxious cascade that leads to irreversible neuronal degeneration and memory impairment in older adults. Recent advances in Aβ seeding studies offer a promising avenue for exploring the mechanisms underlying amyloid deposition and the complex pathological features of AD. However, the extent to which inoculated Aβ seeds can induce reproducible and reliable pathological manifestations remains unclear due to significant variability across studies. In this review, we will discuss several factors that contribute to the induction or acceleration of amyloid deposition and consequent pathologies. Specifically, we focus on the diversity of host animals, sources and recipe of Aβ seeds, and inoculating strategies. By integrating these key aspects, this review aims to offer a comprehensive perspective on Aβ seeding in AD and provide guidance for modeling AD pathogenesis through the exogenous introduction of Aβ seeds.