Dementia affects one-third of all people older than 65 years in the United States. The most common cause of dementia is Alzheimer鈥檚 disease, a progressive, irreversible brain disease that results in impaired cognitive functioning and other behavioral changes. Humans are considered uniquely susceptible to Alzheimer鈥檚 disease, potentially due to genetic differences, changes in brain structure and function during evolution, and an increased lifespan.
However, a new study published August 1 in Neurobiology of Aging provides the most extensive evidence of Alzheimer鈥檚 disease brain pathology in a primate species to date. Researchers from 小黄片视频鈥檚 College of Arts and Sciences, along with colleagues from the George Washington University, Yerkes National Primate Research Center, Georgia State University, Barrow Neurological Institute, and the Icahn School of Medicine at mount Sinai, found that the brains of aged chimpanzees, our closest living relatives, show pathology similar to the human Alzheimer鈥檚 disease brain.
This research adds to a growing number of studies using an evolutionary perspective to identify differences between humans and chimpanzees that could lead to potential targets for therapeutic interventions in humans.
鈥淰ery few studies have investigated Alzheimer鈥檚 disease pathology in chimpanzees, the species closest in phylogeny and most genetically related to humans,鈥 said senior author Mary Ann Raghanti, Ph.D., Associate Professor and Interim Chair of Anthropology at 小黄片视频. 鈥淏rain samples from great apes, particularly aged individuals, are incredibly scarce, so a study of this size is rare.鈥
Dysfunction of two proteins, amyloid beta and tau, plays a role in the development of Alzheimer鈥檚 disease. In healthy brains, amyloid beta is degraded and eliminated, but in Alzheimer鈥檚 disease, overproduction and disrupted clearance of the protein results in the formation of plaques between brain cells called neurons. Amyloid beta in the form of insoluble plaques and soluble peptides initiates changes in tau, another protein found mostly in neurons, that destabilizes the cell鈥檚 skeleton. In Alzheimer鈥檚 disease, alterations in tau lead to the formation of neurofibrillary tangles and cell death. These neuronal changes result in the onset of dementia.
Analysis of the brain samples for this study began in 2013 in Raghanti鈥檚 lab at 小黄片视频. The brains were provided by the National Chimpanzee Brain Resource, which collects the brains of chimpanzees that have died from natural causes at zoos and research centers. The collection started in the mid- 1990s for what was then called the Great Ape Aging Project. The National Chimpanzee Brain Resource is supported by the National Institutes of Health (NIH) and is operated in partnership by the George Washington University, Georgia State and Yerkes National Primate Research Center.
By examining brain regions most affected by Alzheimer鈥檚 disease pathology in humans, the group demonstrated that amyloid beta plaques and blood vessels were present in all 20 aged chimpanzee brains. Similar to humans, increasingly larger volumes of amyloid beta plaques and blood vessels were found with greater age.
鈥淚nterestingly, though, amyloid beta deposition was higher in blood vessels than in plaques, and this correlated with increases in tau lesions,鈥 said Melissa Edler, Ph.D., lead author and former doctoral student in biomedical sciences at 小黄片视频. 鈥淭his suggests that amyloid buildup in the brain鈥檚 blood vessels precedes plaque formation in chimpanzees.鈥
These findings differ from what we see in humans. While approximately 80 percent of Alzheimer鈥檚 disease patients also have cerebral amyloid angiopathy, or amyloid beta deposits in the brain鈥檚 blood vessels that increase the risk for stroke and dementia, the predominant amyloid beta pathology is plaques. Tau lesions also were found in the forms of neurofibrillary tangles and clusters of tau-positive neurites (i.e., pieces of dying neurons).
鈥淣eurofibrillary tangles are observed in Alzheimer鈥檚 disease patients, but the tau-immunoreactive neuritic clusters in the neocortex appear specific to chimpanzees,鈥 said Patrick R. Hof, M.D., Regenstreif Professor and Vice-Chair of Neuroscience at Icahn School of Medicine at Mount Sinai. 鈥淭he presence of amyloid and tau pathology in aged chimpanzees indicates these Alzheimer鈥檚 disease lesions are not specific to the human brain as generally believed.鈥
鈥淲hether these pathologies play a key role in age-related cognitive decline requires continued investigation of this species,鈥 said Elliott Mufson, Ph.D., Professor and Greening Chair in Aging at the Barrow Neurological Institute.
鈥淲e initiated the Great Ape Aging Project 20 years ago because we saw an aging chimpanzee population under human care that would need geriatric attention for disorders similar to those affecting aging humans,鈥 said Joseph Erwin, Ph.D., Research Professor of Anthropology at the George Washington University.