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J Comp Neurol. 2018 Dec 22. doi: 10.1002/cne.24610. [Epub ahead of print]

Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees.

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Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, Ohio.
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio.
Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, Georgia.
MAEBIOS, Alamogordo, New Mexico.
Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, District of Columbia.
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Departments of Neurobiology and Neurology, Barrow Neurological Institute, Phoenix, Arizona.
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
New York Consortium in Evolutionary Primatology, New York, New York.


Astrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD-type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify GFAP-immunoreactive astrocyte density and soma volume in layers I, III, and V of the prefrontal and middle temporal cortex, as well as in hippocampal fields CA1 and CA3. We found that the patterns of astrocyte activation in the aged chimpanzee brain are distinct from humans. GFAP expression does not increase with age in chimpanzees, possibly indicative of lower oxidative stress loads. Similar to humans, chimpanzee layer I astrocytes in the prefrontal cortex are susceptible to AD-like changes. Both prefrontal cortex layer I and hippocampal astrocytes exhibit a high degree of astrogliosis that is positively correlated with accumulation of amyloid beta and tau proteins. However, unlike humans, chimpanzees do not display astrogliosis in other cortical layers. These results demonstrate a unique pattern of cortical aging in chimpanzees and suggest that inflammatory processes may differ between humans and chimpanzees in response to pathology.


Alzheimer's disease; RRID: AB_2109645; RRID: AB_223647; RRID: AB_2313952; RRID: AB_2314223; aging; astrocytes; cerebral cortex; chimpanzees; hippocampus; prefrontal cortex; stereology


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