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.
Neuropathology is assessed through visualization of the markers that have been characterized in human dementia:
β-amyloid-containing plaque deposition
plaques associated with ubiquitinated proteins
plaques associated with ApoE expression