Elevated adenosine monophosphate deaminase activity in Alzheimer's diseasebrain

Abnormal elevations in ammonia have been implicated in the pathogenesis of Alzheimer's disease. However, the biochemical mechanism(s) leading to incre ased ammonia in Alzheimer's disease have not yet been identified. A potenti al source of increased ammonia production is adenosine monophosphate (AMP) deaminase, an important enzyme in the regulation of the purine nucleotide c ycle and adenylate energy charge. AMP deaminase activity is expressed in hu man brain and converts AMP to inosine monophosphate with the release of amm onia. We have investigated AMP deaminase activity in postmortem brain tissu e from Alzheimer's dic;ease subjects and age-matched controls. Compared to control brain, Alzheimer's disease brain AMP deaminase activity is 1.6- to 2.4-fold greater in the regions examined-the cerebellum, occipital cortex, and temporal cortex. Similar increases in AMP deaminase protein and mRNA le vels are observed in Alzheimer's disease brain. These results suggest that increased AMP deaminase activity may augment ammonia levels in the brain in Alzheimer's disease. (C) 1998 Elsevier Science Inc.