PD-1 blockers could promote immune response in Alzheimer’s disease

Written by Alice Weatherston

A recent animal study in Nature Medicine has highlighted the potential efficacy of an immune system-activating cancer medication to improve memory and cognitive ability in Alzheimer’s disease and potentially other neurodegenerative diseases. The study also indicates possibilities for the reduction of key disease-related pathology such as amyloid plaques.
The study, carried out on mouse models of Alzheimer’s disease, suggests immune-checkpoint blockade as a mechanism for therapy. Specifically, the research team based at the Weizmann Institute of Science (Rehovot, Israel) treated mice with Programmed death-1 (PD-1) blockers, recently approved for use in cancer by the US-FDA, that target the PD-1 immune-checkpoint pathway.

Mice treated twice with PD-1 blockers over three days exhibited improved memory performance and reduced amyloid plaques, as well as a reduction in neuroinflammation one month following treatment in comparison to mice that received either a placebo or no treatment at all.

In mice that received two treatment sessions of three days over two consecutive months an even more notable improvement in learning, memory and pathology was identified.

The team led by Michal Schwartz (Weizmann Institute of Science) believe that PD-1 blockers may help to promote the recruitment of immune cells into the brain through an interferon-γ–dependent systemic immune response, consequently impacting the removal of amyloid plaques and the improvement in cognitive ability.

Dr Doug Brown (Alzheimer’s Society) commented: “It’s early days yet, but this study in mice gives us an indication that activating certain immune cells could be a potential way to clear the toxic build-ups of amyloid, one of the hallmarks of Alzheimer’s disease.”

Sources: Medical News Today http://www.medicalnewstoday.com/releases/305194.php?tw; Baruch K et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Nature Medicine doi:10.1038/nm.4022 (2016).