Aging rhesus macaques display distinct fluid proteomic signatures of senescence and neuropathology

Researchers profiled plasma and cerebrospinal fluid from 66 rhesus macaques across adult, pre-geriatric, and geriatric ages using targeted proteomics. They also evaluated brain tissue through immunohistochemistry and benchmarked findings against human reference samples. Plasma showed broader age-associated protein differences than cerebrospinal fluid. Markers of neurosenescence, including neurofilaments, GFAP, and TREM2, mirrored patterns seen in human aging. Systemic inflammatory and metabolic proteins, such as IL6 and GDF15, were higher in older animals. In brain tissue, geriatric macaques developed extensive amyloid deposits with sparse tau pathology. Notably, plasma amyloid-beta and phosphorylated tau tracked age and cortical amyloid burden more closely than cerebrospinal fluid markers did. Older macaques also formed distinct subgroups based on cerebrospinal fluid proteomes that chronological age alone could not explain.