AMYLOID BETA PROTEIN IN CSF AND FAMILIAL AGGREGATION IN ALZHEIMER'S DISEASE

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The presence of Abeta in CSF has a number of exciting implications for understanding Alzheimer's disease. Although data already gathered makes it highly unlikely that Abeta in CSF will be a diagnostic test for Alzheimer's disease, it may nonetheless, be useful in elucidating some of the heterogeneity that exists in the disease. Specifically, one goal of this study is to determine whether Alzheimer's disease probands with higher concentrations of Abeta have first degree relatives with a different morbid risk for Alzheimer's disease than the first degree relatives or probands with a lower concentration of Abeta, or alternatively, whether the age of onset of progressive dementia in first degree relatives can be differentiated by CSF Abeta concentrations. To achieve these goals, CSF will be obtained from Alzheimer's patients in whom the first degree relatives will be evaluated through the family history method to determine the incidence of Alzheimer's disease and related dementias, and age of onset. CSF Abeta will be measured in the laboratory of Steven Younkin at Case Western Reserve. Dr. Younkin's current antibody identifies the 40,41,42 and 43 amino acid sequences of Abeta peptides. However, work at Case Western Reserve will be directed toward developing a specific antibody that can differentiate the 40 vs. 41 and 42 amino acid sequences to determine if either sequence is more revealing than measurements of the combined 4kDa proteins.