Neuropsychology of Cognitive Aging in the Rhesus Monkey
Patrick R. Hof
Neurobiology of Aging Laboratories and Fishberg Research Center for
Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
In the context of the Great Ape Aging Project, we have initiated a
large-scale neuropathological survey of brain aging in great apes
using detailed mapping and stereologic methods focusing on regions
that are severely affected in Alzheimer's disease in human. We
collected brain specimens of chimpanzees (1 to 58 years old),
gorillas (10 to 50 years old), and orangutans (10 to 37 years old).
The brains were imaged in a MRI scanner, casts were obtained, and
materials were collected for diagnostic neuropathology. We estimated
the total number and cellular volume of neurons in layer II of the
entorhinal cortex and CA1 field of the hippocampus using stereologic
tools. We observed no apparent neuron loss and no shrinkage of
cellular volume in aged compared to younger animals in all species.
These data are consistent with previous observations on the
entorhinal cortex of old macaque monkeys, where no cell loss has
been observed. Further, we analyzed how possible alterations in
neuron morphology affect subsets of pyramidal neurons forming short
and long projections using retrograde transport, intracellular
injection of Lucifer Yellow, and 3-dimensional reconstruction in 12
macaque monkeys 6 to 38 years old. There was a significant decrease
in spine density in both apical (p<0.001) and basal (p<0.005)
dendritic arbors in long projection neurons and a less consistent
decrease (p<0.05) in short projection neurons. This suggests that
spine density in corticocortical projection neurons is a sensitive
indicator of cortical aging. In conclusion, it appears that brain
aging differs considerable in monkeys and great apes compared to
humans, where age-related neuronal loss occurs in the entorhinal
cortex even in individuals with preserved intellectual and cognitive
functions. Whereas aging great apes may show some cognitive
deficits, such changes may be due to rather subtle molecular
alterations in the morphological and molecular integrity of neurons
subserving identifiable neocortical association circuits, suggesting
that neuronal subsets prone to neurodegeneration in aging and
dementia have evolved selectively in humans. Supported by NIH
grants AG14308, AG05138, AG02219, AG06647, and NYCEP and MSSM.
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