Phenylethanolamine N-methyltransferase activity is decreased in Alzheimer's disease brains

Phenylethanolamine N-methyltransferase (PNMT) is the rate-limiting enzyme involved in the synthesis of epinephrine and a specific marker for epinephrine neurons. We have previously described the stability of this enzyme in a variety of pre- and postmortem conditions in human brain autopsy specimens and demonstrated its presence in areas of the human brain that are associated with memory and attention. We now report on 5 patients with Alzheimer's disease (AD) who had a decrease in PNMT activity of 37 to 48% in areas of the brain affected by the disease but not in the cerebellum, an area of the brain unaffected by the disease. The degree of decrease in PNMT activity in the hippocampus correlated significantly with the degree of dementia. We have provided direct immunochemical evidence that the decrease in PNMT activity in AD is due to the loss of this specific enzyme protein.