Potential Off-Target Interaction of the Amyloid PET Imaging Tracer PiB with Acetylcholinesterase.

ABSTRACT: Pittsburgh compound B (PiB) is a widely used Positron Emission Tomography (PET) tracer for detecting amyloid-β (Aβ) deposits in Alzheimer's disease (AD). While PiB is assumed to bind selectively to Aβ, emerging evidence suggests off-target interactions that may complicate PET signal interpretation. Here, we report that PiB can interact with acetylcholinesterase (AChE), a key enzyme in the cholinergic system. Similarity screening identified the AChE ligand thioflavin T (ThT) as the top structural analogue of PiB. Docking studies and molecular dynamics simulations showed that PiB stably binds the peripheral anionic site (PAS) of AChE, with binding energies comparable to ThT and clinically relevant AChE inhibitors. In vitro fluorescence-based assays confirmed this interaction and sugge

SUBMITTER: Granzotto A 

PROVIDER: S-EPMC12547588 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature