Amyloid-β Seeds in Alzheimer's Disease: Research Challenges and Implications

The amyloid cascade hypothesis, proposed over 30 years ago, places amyloid-β (Aβ) at the center of Alzheimer's disease (AD) pathogenesis. Though controversial, recent clinical successes with Aβ-targeting therapies have reinforced its importance. However, these treatments have shown only modest clinical benefits in line with a two-stage AD progression: an early phase driven by Aβ-seed and a later phase that progresses at least partly independently of Aβ. Evidence of Aβ seed transmission in humans raises both therapeutic potential and biosafety concerns. This review explores current understanding of Aβ seeds, including challenges in studying such seeds, model systems to study Aβ seeds, and biosafety issues when working with Aβ seeds.