Decreased levels of beta-amyloid (A beta) 1-42 in cerebrospinal fluid (CSF) are characteristic for Alzheimer's disease (AD) and are also evident in Creutzfeldt-Jakob disease (CJD). A beta plaques are thought to be responsible for this decrease in AD patients, whereas such A beta plaques are rarely seen in CJD. To investigate the A beta pattern in brain and CSF of neuropathologically confirmed CJD and AD patients we used an electrophoretic method to investigate A beta peptide fractions which are not accessible to ELISA and immunohistochemistry. We analyzed A beta peptides in the CSF of autopsy-confirmed CJD and AD patients and the corresponding brain homogenates using a quantitative urea-based A beta electrophoresis immunoblot (A beta-SDS-PAGE/immunoblot).The CSF A beta 1-42 decrease correlated with the brain A beta load in AD, but not in CJD. There was no difference in the soluble fractions of brain homogenate in AD and CJD. We therefore conclude that different mechanisms in AD and CJD are responsible for the A beta 1-42 decrease in the CSF.