Neuropathology and Biomarker Correlates of Late Onset Alzheimer's Disease in Aged Old World Monkeys.

This article focuses on the use of spontaneously aged Old World monkeys (OWMs)—including rhesus macaques, cynomolgus macaques, and African green monkeys—as models for studying preclinical Alzheimer's disease (AD). OWMs exhibit age-related amyloid-β (Aβ) plaque deposition and phosphorylated tau (pTau) pathology resembling early Braak stages of human AD, accompanied by fluid biomarker changes consistent with Core 1 AD diagnostic criteria, although amyloid and tau PET imaging remains unsuccessful in these animals. Unlike humans, OWMs show minimal hippocampal atrophy, limited neurofibrillary tangle formation, and reduced expression of senescence markers, suggesting differences in biological brain aging and fewer neuropathologic comorbidities. These features position OWMs as valuable models for investigating early AD pathophysiology, biomarker discovery, and the effects of therapeutics or comorbidities such as diabetes on brain aging.