Review Volume 16, Issue 20 pp 13145—13171
Brain aging and Alzheimer’s disease, a perspective from non-human primates
- 1 Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain
- 2 Reial Acadèmia de Medicina de Catalunya, Barcelona, Spain
Received: March 9, 2024 Accepted: June 3, 2024 Published: October 29, 2024
https://doi.org/10.18632/aging.206143How to Cite
Copyright: © 2024 Isidro. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Brain aging is compared between Cercopithecinae (macaques and baboons), non-human Hominidae (chimpanzees, orangutans, and gorillas), and their close relative, humans. β-amyloid deposition in the form of senile plaques (SPs) and cerebral β-amyloid angiopathy (CAA) is a frequent neuropathological change in non-human primate brain aging. SPs are usually diffuse, whereas SPs with dystrophic neurites are rare. Tau pathology, if present, appears later, and it is generally mild or moderate, with rare exceptions in rhesus macaques and chimpanzees. Behavior and cognitive impairment are usually mild or moderate in aged non-human primates. In contrast, human brain aging is characterized by early tau pathology manifested as neurofibrillary tangles (NFTs), composed of paired helical filaments (PHFs), progressing from the entorhinal cortex, hippocampus, temporal cortex, and limbic system to other brain regions. β-amyloid pathology appears decades later, involves the neocortex, and progresses to the paleocortex, diencephalon, brain stem, and cerebellum. SPs with dystrophic neurites containing PHFs and CAA are common. Cognitive impairment and dementia of Alzheimer’s type occur in about 1-5% of humans aged 65 and about 25% aged 85. In addition, other proteinopathies, such as limbic-predominant TDP-43 encephalopathy, amygdala-predominant Lewy body disease, and argyrophilic grain disease, primarily affecting the archicortex, paleocortex, and amygdala, are common in aged humans but non-existent in non-human primates. These observations show that human brain aging differs from brain aging in non-human primates, and humans constitute the exception among primates in terms of severity and extent of brain aging damage.