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Medical College of Georgia Brain Bank
Human Primates
Under development.
Non-Human Primates
The primary purpose for the Animal Behavior Center (ABC) is the development
of novel therapeutic agents for the improvement of attention, learning, and
memory in cognitively impaired humans. More recently, work has centered on
the problems related to age-dependent memory impairment for which
task-impaired aged primates are perhaps the most appropriate animal model.
Over the past 8 years a number of our young and aged monkeys have been
euthanized or have died of natural causes, and their brains removed and
processed under highly controlled conditions. Dissected brain samples are
either flash frozen in liquid nitrogen, or formalin or alcohol fixed. All
brain samples are carefully cataloged and stored in our non-human primate
brain bank. Therefore, our program is almost unique in the world, in that we
maintain a behavioral data base on the cognitive status of each animal prior
to death, which can then be correlated with neurohistological and
neurochemical changes in the brain. We have banked over 20 such primate
brains.
Rationale: The ability to correlate disease
status with post mortem identification of neuropathology has provided for
the rational approach to a number brain disorders, most notably for the
modern treatment of Parkinson’s disease. This situation is much more
difficult for the cognitive disorders because it is virtually impossible to
identify and obtain post mortem tissue from the early stages of Alzheimer’s
disease, or even age-related cognitive impairment. Brain tissue is usually
only available after a long course of disease; and at autopsy it is usually
difficult, if not impossible, to fix tissue immediately after death. The
development of post mortem artifacts in autopsy tissue has limited
investigation into the etiology of cognitive disorders.
By using a primate model of age-dependent cognitive impairment and with the
ability to rapidly and uniformly fix autopsied brain samples, questions
regarding the neuropathological, anatomical, and neurochemical alterations
that occur along with the behavioral changes associated with aging can be
directly assessed. Under these conditions it should be possible to identify
early neuropathological or neurochemical changes that are responsible for
the cognitive impairment. This has not been possible in human studies. The
identification of early changes in brain structure and function would permit
a better understanding of the initiating factors and result in new
therapeutic approaches that could delay or terminate the disease process. In
the least, our studies would determine whether neurochemical alterations
precede or occur concomitantly with the onset of neuropathological changes.
The development of neurochemical changes prior to neuropathological changes
would support the concept that early intervention could alter the course of
the disease.
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Neuropathology is assessed through visualization of
the markers that have been characterized in human dementia:
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β-amyloid-containing plaque deposition
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plaques associated with ubiquitinated proteins
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plaques associated with ApoE expression
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