Alzheimer's disease (AD)-associated protein is present in brain and cerebrospinal fluid of patients with AD but not in adult, nondemented, normal controls. This protein may represent an abnormal epitope of the "tau" microtubule-associated protein and has been detected before the appearance of senile plaques and neurofibrillary tangles. The amount of AD-associated protein in the frontal and temporal cortices in 93 cases of neuropathologically confirmed AD was compared with the amount that was present in 20 cases without AD. The amount of AD-associated protein was significantly increased in the cases of AD for both brain regions compared with that in the cases without AD. The presence of high levels of this protein is a useful adjunct, postmortem marker of the presence of AD and may eventually lead to tests that allow early detection of individuals at risk for this disease.