The objective of this research is to perform pilot studies aimed at the development of an in vitro, laboratory diagnostic test for Alzheimer's disease (AD). AD is a progressive and incapacitating form of dementia which occurs in the presenile and senile periods, and it is a common, important mental health problem. Currently, there is no laboratory test for AD, and subjects must be screened for psychiatric disorders, especially depression, and for neurological disorders, such as multi-infarct dementia and parkinsonism. The clinical diagnosis of AD is made by exclusion and on the basis of clinical judgement and psychological testing. It is at best correct about 70% of the time, and it is generally agreed that there is need for a diagnostic test for AD. A definitive diagnosis of AD can only be made at present by the histopathological examination of brain tissue, generally at autopsy. This project will study three groups of subjects (at least 10-15 per group): those with the clinical diagnosis of AD, age-matched controls without neuropsychiatric disease and controls with other neuropsychiatric disorders. The clinical findings will be correlated initially with the results of tests on cerebrospinal fluid (CSF). Possibly, correlation with autopsy findings will be possible in some cases. The tests will utilize four murine monoclonal antibodies that were recently produced by this laboratory against a normal rabbit brain fraction. The antibodies all react with Alzheimer neurofibrillary tangles, abnormal structures which are characteristic features of the brain pathology of AD. Preliminary experiments with quantitative inhibition, enzyme-linked immunosorbent (ELISA) assays and a small group of CSFs have shown promise that the tests can reveal differences between AD and normal subjects. In the proposed pilot studies, ELISA assays will be used to test a larger series of CSFs from AD and control subjects. Studies to improve the assays will be performed. The possibility will be investigated that the tests can also be applied to detect differences in blood serum or urine between AD subjects and controls. Additionally, the feasibility of detecting possibly unique, antibody-reactive material in AD CSF will be tested by gel electrophoresis and immunoblotting or immunoprecipitation experiments. If these pilot studies confirm and extend the preliminary findings with these monoclonal antibodies, this will indicate that the antibodies should be useful for developing a laboratory diagnostic test for AD. The optimal test can be determined in future work and utilized for a more extensive clinical evaluation.
