We describe widespread serum amyloid P (AP) immunoreactivity in cerebral lesions including neurofibrillary tangles, senile plaques, and vessels in Alzheimer's disease (AD). To elucidate the mechanisms of its origin in cerebrospinal fluid and localization in brain, we searched for AP mRNA by the polymerase chain reaction. Our findings show that with the exception of liver, AP mRNA was not detectable in any of the brain regions tested or choroid plexus. These observations support extravasation or transport of this serum protein across the blood-brain barrier or the blood-cerebrospinal fluid barrier in the brain of subjects with AD.