Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: A model of early Alzheimer's disease?

Alzheimer's disease (AD) is the most common progressive form of dementia in the elderly. Two major neuropathological hallmarks of AD include cerebral deposition of amyloid-beta protein (Aβ) into plaques and blood vessels, and the presence of neurofibrillary tangles in brain. In addition, activated microglia and reactive astrocytes are often associated with plaques and tangles. Numerous other proteins are associated with plaques in human AD brain, including Apo E and ubiquitin. The amyloid precursor protein and its shorter fragment, Aβ, are homologous between humans and non-human primates. Cerebral Aβ deposition has been reported previously for rhesus monkeys, vervets, squirrel monkeys, marmosets, lemurs, cynomologous monkeys, chimpanzees, and orangutans. Here we report, for the first time, age-related neuropathological changes in cotton-top tamarins (CTT, Saguinus oedipus), an endangered non-human primate native to the rainforests of Colombia and Costa Rica. Typical lifespan is 13-14 years of age in the wild and 15-20+ years in captivity. We performed detailed immunohistochemical analyses of Aβ deposition and associated pathogenesis in archived brain sections from 36 tamarins ranging in age from 6-21 years. Aβ plaque deposition was observed in 16 of the 20 oldest tamarins (>12 years). Plaques contained mainly Aβ42, and in the oldest animals, were associated with reactive astrocytes, activated microglia, Apo E, and ubiquitin-positive dystrophic neurites, similar to human plaques. Vascular Aβ was detected in 14 of the 20 aged tamarins; Aβ42 preceded Aβ40 deposition. Phospho-tau labeled dystrophic neurites and tangles, typically present in human AD, were absent in the tamarins. In conclusion, tamarins may represent a model of early AD pathology.