Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

Abstract

At later ages, humans have high risk of developing Alzheimer disease (AD) which may afflict up to 50% by 90 years. While prosimians and monkeys show more substantial changes, the great apes brains examined show mild neurodegenerative changes. Compared with rodents, primates develop and reproduce slowly and are long lived. The New World primates contain some of the shortest as well as some of the longest-lived monkey species, while the prosimians develop the most rapidly and are the shortest lived. Great apes have the largest brains, slowest development, and longest lives among the primates. All primates share some level of slowly progressive, age-related neurodegenerative changes. However, no species besides humans has yet shown regular drastic neuron loss or cognitive decline approaching clinical grade AD. Several primates accumulate extensive deposits of diffuse amyloid-beta protein (Aβ) but only a prosimian-the gray mouse lemur-regularly develops a tauopathy approaching the neurofibrillary tangles of AD. Compared with monkeys, nonhuman great apes display even milder brain-aging changes, a deeply puzzling observation. The genetic basis for these major species differences in brain aging remains obscure but does not involve the Aβ coding sequence which is identical in nonhuman primates and humans. While chimpanzees merit more study, we note the value of smaller, shorterlived species such as marmosets and small lemurs for aging studies. A continuing concern for all aging studies employing primates is that relative to laboratory rodents, primate husbandry is in a relatively primitive state, and better husbandry to control infections and obesity is needed for brain aging research.

Comparative Pathology of Aging Great Apes

“…45,77,78 Decline in cognitive function in aging humans ranges from mild forgetfulness and slower data processing to severe dementia. Dementia is a syndrome in which thinking skills are impaired to the point that the individual can no longer perform daily functions.…”

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

“…Deposits of Aβ protein are apparent with aging in several species, such as non-human primates, dogs, and bears [166][167][168]. Studies of APP transgenic mouse models of AD have shown that there is an abrupt spine loss and neurite dystrophy in the neighborhood of amyloid plaques [169][170][171].…”

Age-related effects in the neocortical organization of chimpanzees: Gray and white matter volume, cortical thickness, and gyrification

“…Nonhuman primates are of particular interest for studying the neurobiological correlates of aging because of their close phylogenetic relationship with humans (Finch and Austad, 2012). Nonhuman primates are often used as models to understand the effects of aging independent of the cellular changes that cause age-related neurodegenerative disorders commonly seen in humans such as Alzheimer's disease (Gearing et al, 1996; Kimura et al, 2003; Koo et al, 2012; Lemaitre et al, 2012; Sherwood et al, 2011; Squire et al, 1988).…”