Aβ oligomer elimination decreases tau oligomer concentration in CSF and enhances cognition in cognitively impaired aged Beagle dogs ‐ a model of sporadic Alzheimer’s disease

Disease‐modifying therapies to treat Alzheimer’s disease (AD) are of fundamental interest for aging humans, societies, and health care systems. More and more data suggest that the toxic protein assemblies of Aβ and tau behave prion like. The drug candidate RD2 (alias PRI‐002) has been developed to directly disassemble and disrupt toxic Aβ oligomer prions. The anti‐prionic compound is BBB penetrable and has demonstrated target engagement in vitro, ex vivo and in vivo. Treatment with RD2 has yielded improved cognition and deceleration of neurodegeneration in three different transgenic mouse models in three different laboratories. Cognitively impaired aged Beagle dogs are one of the very few non‐transgenic AD animal models that may simulate the situation of spontaneous late onset AD, i.e. sporadic AD, which is the most common form of AD in humans. The aim of this study was to investigate the efficacy of RD2 to enhance short‐term memory and cognition in cognitively impaired aged Beagle dogs ‐ a non‐transgenic model of sporadic AD.