Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees
Aging; Alzheimer's disease; astrocytes; cerebral cortex; chimpanzees; hippocampus; prefrontal cortex; RRID: AB2109645; RRID: AB223647; RRID: AB2313952; RRID: AB2314223; stereology
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.
Munger Emily L; Edler Melissa K; Hopkins William D; Ely John J; Erwin Joseph M; Perl Daniel P; Mufson Elliott J; Hof Patrick R; Sherwood Chet C; Raghanti Mary Ann
The Journal of Comparative Neurology
2019
2019-05
<a href="http://doi.org/10.1002/cne.24610" target="_blank" rel="noreferrer noopener">10.1002/cne.24610</a>
Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease.
*Alzheimer's disease; *Amyloid-beta protein; *Chimpanzee; *Neurofibrillary tangle; *Primate; *Tau; Aging/*metabolism/*pathology; Alzheimer Disease/*metabolism/*pathology; Amyloid beta-Peptides/metabolism; Animals; Brain/*metabolism/*pathology; Female; Humans; Male; Neurofibrillary Tangles/metabolism/pathology; Pan troglodytes; tau Proteins/metabolism
Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Abeta) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Abeta and tau lesions in brain regions affected by AD in humans. Abeta was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Abeta deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Abeta plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain.
Edler Melissa K; Sherwood Chet C; Meindl Richard S; Hopkins William D; Ely John J; Erwin Joseph M; Mufson Elliott J; Hof Patrick R; Raghanti Mary Ann
Neurobiology of aging
2017
2017-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neurobiolaging.2017.07.006" target="_blank" rel="noreferrer noopener">10.1016/j.neurobiolaging.2017.07.006</a>
Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees.
aging; Alzheimer's disease; astrocytes; cerebral cortex; chimpanzees; hippocampus; prefrontal cortex; RRID: AB2109645; RRID: AB223647; RRID: AB2313952; RRID: AB2314223; stereology
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
Munger Emily L; Edler Melissa K; Hopkins William D; Ely John J; Erwin Joseph M; Perl Daniel P; Mufson Elliott J; Hof Patrick R; Sherwood Chet C; Raghanti Mary Ann
The Journal of comparative neurology
2018
2018-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/cne.24610" target="_blank" rel="noreferrer noopener">10.1002/cne.24610</a>
Microglia changes associated to Alzheimer's disease pathology in aged chimpanzees.
Alzheimer's disease; amyloid beta protein; chimpanzee; microglia; neurofibrillary tangle; neuroinflammation; RRID: AB223647; RRID: AB2313890; RRID: AB2313952; RRID: AB2315150; RRID: AB839504
In Alzheimer's disease (AD), the brain's primary immune cells, microglia, become activated and are found in close apposition to amyloid beta (Abeta) protein plaques and neurofibrillary tangles (NFT). The present study evaluated microglia density and morphology in a large group of aged chimpanzees (n = 20, ages 37-62 years) with varying degrees of AD-like pathology. Using immunohistochemical and stereological techniques, we quantified the density of activated microglia and morphological variants (ramified, intermediate, and amoeboid) in postmortem chimpanzee brain samples from prefrontal cortex, middle temporal gyrus, and hippocampus, areas that show a high degree of AD pathology in humans. Microglia measurements were compared to pathological markers of AD in these cases. Activated microglia were consistently present across brain areas. In the hippocampus, CA3 displayed a higher density than CA1. Abeta42 plaque volume was positively correlated with higher microglial activation and with an intermediate morphology in the hippocampus. Abeta42-positive vessel volume was associated with increased hippocampal microglial activation. Activated microglia density and morphology were not associated with age, sex, pretangle density, NFT density, or tau neuritic cluster density. Aged chimpanzees displayed comparable patterns of activated microglia phenotypes as well as an association of increased microglial activation and morphological changes with Abeta deposition similar to AD patients. In contrast to human AD brains, activated microglia density was not significantly correlated with tau lesions. This evidence suggests that the chimpanzee brain may be relatively preserved during normal aging processes but not entirely protected from neurodegeneration as previously assumed.
Edler Melissa K; Sherwood Chet C; Meindl Richard S; Munger Emily L; Hopkins William D; Ely John J; Erwin Joseph M; Perl Daniel P; Mufson Elliott J; Hof Patrick R; Raghanti Mary Ann
The Journal of comparative neurology
2018
2018-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/cne.24484" target="_blank" rel="noreferrer noopener">10.1002/cne.24484</a>