Early Alzheimer's disease‐like reductions in gray matter and cognitive function with aging in nonhuman primates

Abstract

Introduction Age‐related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline. Methods Using structural magnetic resonance imaging and cognitive assessments, we examined the relationships among age, cognitive performance, and neuroanatomy in 48 vervet monkeys (Chlorocebus aethiops sabaeus) ranging from young adults to very old. Results We found negative associations of age with cortical gray matter volume (P = .003) and the temporal‐parietal cortical thickness meta‐region of interest (P = .001). Additionally, cortical gray matter volumes predicted working memory at approximately 1‐year follow‐up (correct trials at the 20s delay [P = .008]; correct responses after longer delays [P = .004]). Discussion Cortical gray matter diminishes with age in vervets in regions relevant to AD, which may increase risk of cognitive impairment. This study lays the groundwork for future investigations to test therapeutics to delay or slow pathological decline.

Preliminary PET Imaging of Microtubule-Based PET Radioligand [11C]MPC-6827 in a Nonhuman Primate Model of Alzheimer’s Disease

“…We focused our image analysis on those commonly studied brain regions most affected by aging and AD-related pathology in NHPs , and humans . To identify these regions, magnetic resonance imaging (MRI) was used to acquire anatomical images of all four monkeys.…”

Alzheimer’s Disease: Treatment Strategies and Their Limitations

“…Recently, Latimer et al showed that vervets and other NHP are promising models for exploring early-stage disease mechanisms and biomarkers and testing new therapeutic strategies [153]. These monkeys have the propensity to develop diseases relevant to humans during aging without genetic handling [154]. However, there are several limitations; vervets show amyloid deposits but do not have neurofibrillary tangles or tauopathy; therefore, they do not present generalized neurodegeneration.…”

Non-human Primate Models of Alzheimer’s Disease

“…80 In vervet monkeys, their cortical grey matter volume and temporal-parietal cortical thickness was negatively associated with age, potentially increasing the risk of cognitive decline. 81 In general, naturally aging NHPs demonstrate human-AD resembling proteopathies, glial activation, but severe brain atrophy and cognitive decline is rarely observed, striking our interest into the protective mechanism preventing severe demented symptoms from occurring.…”

“…75 Similar age-related brain volume changes in young and old vervet monkeys were also reported using MRI. 81 Additionally, MRI has been used to examine amyloid-related imaging abnormalities, a potentially serious side effect in clinical trials for AD that is closely associated with CAA. Aged squirrel monkeys showed both edematous and hyperintense types of amyloid-related imaging abnormalities, accompanied by reactive astrocytosis, microgliosis, infiltration of systemic inflammatory/immune cells, damage to axons and myelin, and hemosiderin deposition.…”