Neuronal vulnerability to brain aging and neurodegeneration in cognitively impaired marmoset monkeys (Callithrix jacchus)

The investigation of neurobiological and neuropathological changes that affect synaptic integrity and function with aging is key to understanding why the aging brain is vulnerable to Alzheimer's disease. We investigated the cellular characteristics in the cerebral cortex of behaviorally characterized marmosets, based on their trajectories of cognitive learning as they transitioned to old age. We found increased astrogliosis, increased phagocytic activity of microglial cells and differences in resting and reactive mi-croglial cell phenotypes in cognitively impaired compared to nonimpaired marmosets. Differences in amyloid beta deposition were not related to cognitive trajectory. However, we found age-related changes in density and morphology of dendritic spines in pyramidal neurons of layer 3 in the dorsolateral pre-frontal cortex and the CA1 field of the hippocampus between cohorts. Overall, our data suggest that an accelerated aging process, accompanied by neurodegeneration, that takes place in cognitively impaired aged marmosets and affects the plasticity of dendritic spines in cortical areas involved in cognition and points to mechanisms of neuronal vulnerability to aging. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

The investigation focuses on the neurobiological and neuropathological changes in synapses and their impact on the vulnerability of the aging brain to Alzheimer's disease. Cellular characteristics in the cerebral cortex of behaviorally characterized marmosets were studied, revealing increased astrogliosis, heightened phagocytic activity of microglial cells, and differences in microglial cell phenotypes between cognitively impaired and non-impaired marmosets. Additionally, age-related changes in dendritic spines were observed in cortical areas associated with cognition. These findings suggest an accelerated aging process and neurodegeneration contributing to neuronal vulnerability in cognitively impaired aged marmosets.