Taurine inhibits apolipoprotein E4 aggregation.

Apolipoprotein E4 (ApoE4) is a major genetic risk factor in many neurodegenerative diseases, yet effective therapeutic strategies targeting its associated pathologies remain unresolved. The aggregation of ApoE4, a key pathological feature, is modulated by tramiprosate and its metabolite 3-sulfopropanoic acid. In this study, we provide mechanistic insights into how taurine, a close chemical analogue of tramiprosate, interacts with ApoE4 and may similarly modulate its aggregation behavior. Using an integrated approach, which included molecular dynamics simulations, static light scattering, mass spectrometry, and cerebral organoid models, we investigated the effects of taurine on ApoE4 aggregation. Our results indicate that taurine effectively prevents ApoE4 aggregation and exerts a partial disaggregating effect on pre-formed aggregates. Notably, taurine modulates molecular and cellular features associated with the ApoE4 isoform, shifting them toward patterns observed in the more benign ApoE3 isoform. These observations are consistent with effects similar to those reported for tramiprosate and 3-sulfopropanoic acid and suggest that taurine influences ApoE4-related molecular mechanisms, particularly in the context of the high-risk ApoE4/E4 genotype.