Cu(ATSM) Boosts P-Glycoprotein 24.1% and Cuts Amyloid-Beta 42% in APP/PS1 Mice

Monash researchers administered Cu(ATSM) for 56 days to APP/PS1 transgenic mice and quantified P-glycoprotein abundance at the blood-brain barrier by Western blot and immunohistochemistry. They measured amyloid-beta load via ELISA and immunohistochemistry and assessed long-term spatial memory in the Morris water maze. The compound also appeared to enhance microglial uptake of plaques, although the precise efflux routes remain unmapped. The findings extend prior observations that P-glycoprotein expression declines early in Alzheimer’s and that copper complexes can modulate neurovascular function. Because Cu(ATSM) has already completed Phase 1 safety testing in Parkinson’s and ALS patients, the pharmacokinetic and toxicology packages are largely reusable, shortening the preclinical-to-clinical timeline compared with novel chemical entities. Nevertheless, the data derive from a single transgenic line, short treatment duration, and surrogate rather than clinical endpoints. No human biomarker or imaging confirmation of P-glycoprotein restoration has yet been reported. Next steps require CSF P-glycoprotein activity measurements and amyloid-PET in a Phase 1b Alzheimer’s cohort to test translatability.