Biomarkers of Inflammation, Neurodegeneration and Age-Associated Cognitive Impairment

Project Summary With a rapidly increasing population of aging Americans, cognitive impairment associated with normative aging, or neurodegenerative diseases including Alzheimer's Disease and other related dementias (ADOD), will place increasing burden on our public health infrastructure. Unfortunately, few effective

screening tools or therapeutic strategies exist, and many patients are refractory to treatment. Recent studies suggest that altered neuroinflammatory signaling may play an important early role in normative aging, and in ADOD, but the mechanisms by which the complex interaction of pro- and anti-inflammatory pathways

change over the lifespan, or modulate cognition, are unclear. For this reason, studies using animal models that closely recapitulate normative human aging, but on a shorter timescale, are desperately needed to test the overall hypothesis that rising levels neuroinflammation occurs prior to neurodegeneration and age-

related cognitive impairment, and represent a potential early marker. To address this need, the central goal of my project will be to query the relationship between markers of neuroinflammation with brain morphology and microstructure, and cognition, in naturally-occurring rhesus macaque model of age-related cognitive

impairment. I will use a combination of ultra-sensitive cerebral spinal fluid (CSF) protein biomarker assays, Positron Emission Tomography (PET) imaging of activated astrocytes and microglia, high-resolution Magnetic Resonance Imaging (MRI) of brain morphology and microstructure, and cognitive assessment for

spatial working memory. The strength of these studies lies in their potential to characterize novel biomarkers of neuroinflammatory and neurodegenerative pathways that are associated with memory impairment, and to identify new potential biomarkers that can serve as screening tools and future therapeutic targets.