Quantitative co‐localization of hyaluronic acid and damaged myelin in the aging rhesus monkey brain

Abstract

Normal aging in the rhesus monkey is characterized by subtle sublethal changes that affect cell function and lead to cognitive impairments even though neurons are not lost. One sublethal change that correlates with cognitive decline is damaged myelin which can lead to action potential failure, decreased trophic factor support, loss of axons and synapses, and ultimately to cognitive decline but the cause of this damage is unknown. Hyaluronic acid (HA) has been shown to interfere with remyelination in various disease models by inhibiting differentiation of oligodendroglia precursor cells. HA has also been shown to increase in the prefrontal cortex of aged rhesus monkeys. We hypothesize that age‐related increases in HA contribute to myelin deterioration by interfering with myelin repair mechanisms. Tissue from behaviorally characterized young and old monkeys is being processed to quantitatively co‐localize HA (HA binding protein histochemistry) with damaged myelin (encephalitogenic peptide antibody) in white matter tracts critical to cognitive functions including learning and memory and executive function. This histological data will be compared with subjects’ cognitive impairment measures to identify the age of onset of significant changes for specific white matter tracts. (Supported by R01AG021133 and P01AG000001)