Alzheimer's disease: A clinical perspective and future nonhuman primate research opportunities

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the sixth leading cause of death and the most common cause of dementia worldwide. Over the last few decades, significant advancements have been made in our understanding of AD by investigating the molecular mechanisms underlying amyloid-β and tau pathology. Despite this progress, no disease-modifying treatments exist for AD, an issue that will exacerbated by the rising costs and prevalence of the disorder. Moreover, effective therapies to address the devastating cognitive and behavioral symptoms are also urgently needed. This perspective focuses on the value of nonhuman primate (NHP) models in bridging the molecular, circuit, and behavioral levels of analysis to better understand the complex genetic and environmental/lifestyle factors that contribute to AD pathogenesis. These investigations could provide an opportunity for translating our understanding of the pathogenesis and physiological mechanisms underlying AD and related disorders into new diagnostic approaches and disease-modifying therapies to prevent disease or restore brain function for symptomatic individuals.

Keywords: Alzheimer’s disease; dementia; nonhuman primates.

Fig. 1.

Aβ-immunoreactive deposits (brown) in the neocortex of a 35-y-old female rhesus monkey. One of a morphologic variety of Aβ plaques is indicated by the arrow, and an Aβ-positive blood vessel (CAA) is indicated by the arrowhead. (Scale bar: 200 μm.)