HEAT-SHOCK-70 MESSENGER-RNA LEVELS IN HUMAN BRAIN - CORRELATION WITH AGONAL FEVER

Systematic review of antemortem clinical information on randomly selec ted Alzheimer disease (AD) patients revealed that similar to 40% of th e patients had a recorded fever of greater than or equal to 39.2 degre es C at or near death. Using isolation and quantitation techniques app ropriate for analysis of human brain mRNAs, we found that low levels o f inducible heat-shock protein 70 (hsp70) mRNAs were present in cerebe llum of afebrile AD patients and that mRNA levels were usually lower i n two brain regions affected in AD, i.e., hippocampus and temporal cor tex. Levels of hsp70 mRNAs were increased three- to 33-fold in cerebel lum of febrile patients compared with levels in patients whose recorde d temperatures were less than or equal to 37.5 degrees C. Levels of hs p70 mRNAs were also increased in hippocampus and cortex of these febri le patients, but to a lesser extent than cerebellum. Heat-shock cognat e 70 (hsc70) mRNAs were present at highest levels in afebrile cerebell um and were also present in the other brain regions. In cerebellum of patients with the highest temperatures, hsc70 mRNAs were induced sever alfold over basal levels. Although there was a low and variable induct ion of hsc70 mRNAs in temporal cortex of these patients, there was no evidence for any induction in hippocampus. Increased heat-shock 70 mRN A levels did not correlate with hypoxia, coma, hypertension, hypoglyce mia, seizures, or medication. These results indicate that a specific a gonal stress, namely fever, can increase the levels of heat shock 70 m RNAs in AD brain; however, there is no evidence to suggest that affect ed regions of AD brain have higher overall levels of these mRNAs. Fail ure to obtain adequate agonal state information could result in inaccu rately identifying short-term stress-related changes in postmortem bra in as neuropathology characteristic of a chronic disease state.