# White Matter Pathology and Infiltrating T cells in the Brain of Cognitively Impaired Aging Rhesus Monkeys > **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $206,250 ## Abstract ABSTRACT Normal aging occurs in the absence of frank neurodegenerative disease but nevertheless is characterized by impairments in learning, memory and executive function. The rhesus monkey is a valuable model of normal aging as it does not suffer from Alzheimer's Disease (AD) or other neurodegenerative conditions. Yet, the monkey still exhibits patterns of cognitive decline similar to those observed in humans. While cognitive aging was long believed to be due to neuron loss, careful stereologic investigations have confirmed that neurons are not lost. Instead, with age, white matter volume decreases as myelin pathology, in the form of splitting and ballooning of the sheaths, increases. We have previously found that both loss of white matter volume and damage to myelinated fibers correlate with age-related cognitive impairment, but the cause of this pathology is not known. In searching for possible causes, the well documented age-related increases in oxidative stress and inflammation are prime candidates. Several studies from this lab have demonstrated that microglial activation and phagocytosis increase with age and correlate with cognitive decline but it is not clear if this is a response to the pathology or a causative factor. Our recent pilot studies have revealed infiltration of peripheral T cells into the brain white matter raising the possibility that they may cause or exacerbate pathology. In Aim 1, we propose to explore this issue using cryopreserved brain tissue sections collected from 50 behaviorally tested rhesus monkeys of both sexes that range in age from 5 to over 30 years old (human equivalent of 15 to about 90 years of age). Sections will be processed with immunohistochemistry to identify T cells and their subtypes, which will be quantified with stereology by location, frequency and T cell subtype. These results will be correlated with myelin damage by using the recently described SCoRe method (spectral confocal reflectance microscopy). Aim 2 will utilize 6 new behaviorally tested monkeys (3 young and 3 old) from which fresh tissue will be harvested to assess, ex vivo, the function of parenchymal T cells. This will be done by performing RNA sequencing on sorted CD3+ T cells from brain white matter, choroid plexus, and blood to compare differences in RNA phenotype across these environments. Understanding the extent to which T cells from the periphery mirror those that infiltrate the brain may provide novel peripheral biomarkers to assess brain aging. Additionally, we will isolate T cells, stabilize them in culture, and assess their myelin reactivity by exposing them to myelin antigens. All results will be analyzed relative to age, myelin pathology and the severity of cognitive impairment. In addition to an overall increase in parenchymal T cells with age, we expect to identify the inflammatory profiles likely to exacerbate myelin damage. Together, these data should provide insight into a possible role of T cells in age- related mye... ## Key facts - **NIH application ID:** 9851779 - **Project number:** 5R21AG061678-02 - **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS - **Principal Investigator:** Douglas L Rosene - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $206,250 - **Award type:** 5 - **Project period:** 2019-02-01 → 2021-11-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9851779 ## Citation > US National Institutes of Health, RePORTER application 9851779, White Matter Pathology and Infiltrating T cells in the Brain of Cognitively Impaired Aging Rhesus Monkeys (5R21AG061678-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851779. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*