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The Great Ape Aging Project: Contributions to Evolutionary Neurobiology.

Joseph Erwin*, PhD, Division of Neurobiology and Behavior, Bioqual, Inc., Rockville, Maryland, USA, and Foundation for Comparative and Conservation Biology, Frostburg, Maryland, USA; Patrick HOF, MD, Daniel PERL, MD, and Esther NIMCHINSKY**, MD, PhD, Mount Sinai School of Medicine, New York, New York, USA (*Presenter, **Now at Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA)

     The Great Ape Aging Project (GAAP) involves noninvasive study of behavior and health of all four great ape species and postmortem collection of CNS tissues for detailed research on brain anatomy and pathology, with a special focus on evidence of neurodegerative processes such as those seen in human Alzheimer's disease. All the great apes in zoological gardens and research centers in the U.S. who are 40 years of age or older have been enrolled in the project. Methods of conducting cognitive assessments and creating behavioral profiles based on systematic observations are being developed. Nearly 50 great ape brains have been loaned to the project for postmortem evaluation and detailed study. We have initiated a large-scale neuropathology survey of brain aging in great apes using detailed mapping and stereologic methods. The focus is on regions that are severely affected in Alzheimer's disease and are affected early by age-related neuropathology in humans. The total number and cellular volumes of Layer II of the entorhinal cortex (ERC) were examined using stereologic tools in a series of 18 postmortem specimens from chimpanzees ranging in age-at-death from 1 day to 45 years. Unlike humans, no apparent neuronal loss was found in any chimpanzee brain (Erwin, 1999). In anterior cingulate cortex, a type of large neuron (a spindle cell) occurs in humans and is affected in Alzheimer's (about 60% loss). This cell type was found to be unique to humans and great apes. Examination of brains from 28 primate species (including human) and 30 non primate mammal species revealed that this cell type occurs only in humans and great apes. It is sparse in orangutans, more abundant in gorillas, more yet in chimpanzees, and in bonobos, the cells were clustered as in humans (Nimchinsky et al., 1999). The region in which this cell occurs seems to be involved in visual self-awareness, communication, and pain perception. A large pyramidal cell in that area that is similarly distributed and has also been found exclusively in great apes and humans. Stroke damage to this area sometimes causes humans to lose the ability to recognize familiar faces or even their own mirror images. The Comparative Neurobiology of Aging Resource (CNAR) has also been used for detailed studies of brain areas involved in human language (cf. Gannon, et al., 1998). Detailed examination of human and great apes reveal a mosaic of quantitative and qualitative differences. Advanced methods of study allow more than ever before to be learned from the similarities among humans, great apes, and other animals. Collaborative studies using the resource are encouraged. The Comparative Neurobiology of Aging Resource is supported by a generous grant from the National Institute on Aging (AG14308) to Bioqual, Inc., J. Erwin, Principal Investigator.

Erwin, J., Perl, D., Nimchinsky, E., and Hof, P. Stereologic analyses of neuron number and volume in the entorhinal cortex of aged chimpanzees. Society for Neuroscience Abstracts 25(Part 1):105, 1999.
Nimchinsky, E., Gillissen, E., Allman, J., Perl, D., Erwin, J., and Hof, P. A neuronal morphologic type unique to humans and great apes. Proceedings of the National Academy of Sciences 96:5268-5273, 1999.
Gannon, P., Broadfield, D., Kheck, N., Hof, P., Braun, A., and Erwin, J. Brain language area evolution, 1: anatomic expression of Heschl's gyrus and planum temporal asymmetry in great apes, lesser apes, and old world monkeys. Society for Neuroscience Abstracts 24(Part 1): 160, 1998.