We studied levels of amyloid beta-protein precursor (beta PP) in CSF from four patients affected with Gerstmann-Sträussler-Scheinker disease and one asymptomatic gene-carrier from an Indiana kindred. Levels of beta PP were decreased in all affected patients with the lowest levels occurring in the clinically most severely affected patients. Correlation of neuropathology with CSF data in three patients suggested that low beta PP in CSF may be associated with beta PP accumulation in neurites surrounding cortical and cerebellar amyloid deposits.