ABSTRACT NUMBER: ESOC2026LB37 NATURALLY OCCURRING CEREBRAL SMALL VESSEL DISEASE-LIKE PATHOLOGY IN THE BRAIN OF AGING MONKEYS: AN MRI-PATHOLOGIC CORRELATION STUDY

Abstract Background and aims The pathological basis underlying the neuroimaging alterations in arteriolosclerotic cerebral small vessel disease (aCSVD) has not been fully elucidated. Non-human primates (NHPs) are ideal models for aCSVD research. However, few studies systemically investigate the MRI-pathological correlation of aCSVD in aged monkeys. Here, we aimed to explore the aCSVD-like MRI and neuropathology alterations naturally occurring in aging NHPs and to examine their underlying correlations. Methods We conducted 3.0 T MRI and assessed aCSVD-like neuropathology across multiple regions in 10 cynomolgus monkeys, categorized into young (6~7y), middle-aged (12~14y), and aged (21~30y) groups. The cortical thickness, grey and white matter volume were evaluated on MRI in various regions. The lacunes, neuronal loss, white matter lesions, haemosiderin deposits, gliosis and cerebrovascular injuries were evaluated pathologically. Results Lacunes and white matter hyperintensities in MRI corresponded to pathologically found lacunes, myelin loss and axonal damage in the oldest monkey. Decreased cortical thickness in the area 8A, dorsolateral prefrontal cortex, TEO, caudal superior temporal gyrus and visual area 2-4 corresponded to neuronal loss pathologically. aCSVD-like parenchymal lesions and vessel density were associated with age. In the corpus callosum and deep white matter, axonal damage positively correlated with myelin loss, and both were associated with microglia activation. Additionally, haemosiderin deposits correlated with albumin leakage in the corpus callosum and periventricular white matter. Conclusions Our results provide a comprehensive assessment of naturally occurring age-related MRI-pathological findings in aging monkeys and evaluated their associations. This study implies NHPs as ideal models for aCSVD research and clinical translation. Conflict of interest