Amyloid-β degradation in Alzheimer’s disease using SPYTACs

The current anti-Aβ immunotherapy clears amyloid-β (Aβ) deposits from the brain of Alzheimer’s disease (AD) patients but also has raised safety concerns due to frequent adverse effects.

In this study, the researchers developed a next-generation extracellular targeted protein degradation (eTPD) platform, synthetic peptide-programmed lysosome-targeting chimeras (SPYTACs), using entirely synthesized bispecific peptides.

SPYTAC platform harnesses lipoprotein receptor-related protein 1 (LRP1) to drive lysosomal degradation of extracellular amyloid-β in the brain and periphery.

In 5×FAD mice, SPYTAC treatment efficiently degrades amyloid-β, preserves neurons, and improves cognition with reduced neuroinflammation and microhemorrhage with fewer side effects when compared with antibody therapy.

https://www.cell.com/cell/fulltext/S0092-8674(26)00162-5

https://sciencemission.com/Amyloid-%CE%B2-degradation-in-AD-using-SPYTACs