Cinnamon Bud Extract Is a Source of Biomolecules Active against the Aggregation and Condensation of Alzheimer's-Associated Tau Protein

Abnormal accumulation of tau fibrillar aggregates is a hallmark of tauopathies, including Alzheimer's disease. Targeting tau aggregation represents a promising strategy for preventing and treating neurological disorders, especially using natural compounds with favorable safety profiles. In this study, we investigated a hydroalcoholic extract of Cinnamomum cassia buds (BCHE) and its major components, cinnamaldehyde and shikimic acid, for their effects in modulating tau repeat domain aggregation and liquid-liquid phase separation. In vitro results show that BCHE and cinnamaldehyde inhibit tau aggregate maturation, promoting the formation of nonfibrillar, off-pathway species and modulating condensate formation. These alternative aggregates exhibit reduced cytotoxicity in SH-SY5Y neuroblastoma cells and lower seeding capacity than canonical fibrils. BCHE also contains compounds capable of binding preformed tau fibrils. Overall, these findings suggest a novel mechanism by which cinnamon-derived bioactive molecules mitigate tau aggregation and reduce its cellular toxicity, highlighting their potential as neuroprotective agents.