Imipramine binds to Amyloid-β (1-42) monomers in vitro, as shown by NMR spectroscopy

Imipramine is known as an older generation tricyclic antidepressant drug. It has been identified in prior studies that imipramine blocks Apolipoprotein E4 (ApoE4)-induced amyloid-β(Aβ) aggregation and is associated with an improved AD diagnosis [Johnson et al. Alzheimer’s Research & Therapy, 2022 , 14:88]. Using NMR methods such as ¹ H- ¹ H NOESY and Saturation Transfer Difference Spectroscopy, we demonstrate the binding of Aβ monomers to imipramine when the full-length Aβ (1-42) sequence is considered. The more abundant but less toxic form, Aβ (1-40) does not show interaction with imipramine.