The incidence for senile dementia of the Alzheimer type (Alzheimer's Disease) is increasing rapidly. Thus, there is a critical need for understanding the causes of this disease and for developing beneficial therapies for patients afflicted with Alzheimer's Disease. One difficulty that physicians encounter is the inadequate diagnostic methods presently available. Although it is clear that there is major degeneration of cholinergic function in the CNS, there is no test available for indicating such degeneration. In addition, some patients respond to the anticholinesterase, physostigmine, but there is no way to predict responders from non-responders. In this project we propose to measure cholinergic parameters in blood samples from patients with Alzheimer's Disease to identify specific markers of the disease and to identify markers of patients likely to respond to treatment with physostigmine. Two advantages to this project are (1) all measurements are already in use as we have made a similar study of patients with psychiatric disorders, and (2) all cholinergic processes in blood will be measured in every sample rather than making isolated measurements of single processes. In addition, the data will be compared to other approaches used by other members of this program project. The measurements to be made include acetycholinesterase in plasma and red blood cells, pseudocholinesterase in plasma, choline concentration in plasma and red blood cells and the kinetics of erythrocyte choline influx. This comprehensive study of the cholinergic system in samples from a well-defined patient population should allow us to identify specific abnormalities and/or overall patterns of differences among the samples studied.
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