PM20D1-derived treatment induces microglia association with amyloid plaques and improves Alzheimer’s disease pathologies

Here, we describe a new mechanism by which the recently AD-associated Peptidase M20 Domain Containing 1 (PM20D1) instructs microglia to tackle AD. We show that the PM20D1-derived N-oleoyl-Leucine (OLE) improves AD pathologies in two animal models of AD.

OLE induces microglia association with amyloid beta (Aβ) plaques, reduce their size, number and toxicity, and leads to enhanced neuroprotection and cognition. Furthermore, OLE also increases Aβ chemotaxis and clearance in microglia cultures and enhances cell viability in neurons subjected to AD-related stressors. Finally, we also find evidence for a PM20D1- and OLE-mediated microglia association with amyloid plaques and neuroprotection in human AD brains.