Neuropathologic features of AD include neuritic amyloid plaques and tangles in cerebrocortical pathways in the brain. Recent studies have also shown that a heterogenous mixture of GAGs improves cognition in aged rats, and reversed cognitive and neurochemical deficits in patients with AD. Thus, GAGs may be potentially useful in the prevention of AD neuropathology. These Phase I studies will involve a preliminary screen of three new, specific GAGs. They will be tested in an animal model in which astrocytosis and trans-synaptic cytoskeletal and astrogliotic reactions similar to those seen in the AD patient are induced by injection of Abeta 25-35 into the rat amygdala. The GAGs' ability to prevent: (a) aggregation of Abeta; (b) production of abnormal tau immunoreactivity, reactive astrocytosis, and neuronal shrinkage; (c) changes in choline acetyltransferase, cholinesterase, serotonin, and 5HIAA levels; and (d) changes in the size of dendritic arbors and density of dendritic spines of neurons, using Golgi morphometry; will be explored in several brain regions. The objectives of this study are to identify and test prototypic homogenous GAGs that have potential for treatment of AD.
Development of a treatment for senile dementia of the Alzheimer type.
