Acetaminophen: The Case for a Link to Neurodegenerative Diseases

Abstract

Acetaminophen is a centrally acting antipyretic and analgesic which has been used in humans since the 1970’s. It’s use has increased for a variety of reasons including its use for extended periods of time and for chronic pain. Acetaminophen either decreases or depletes the endogenous anti-oxidant glutathione in mammalian cells. Without the protective effects of glutathione, mammalian cell damage or cell death occurs. Neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease and disorders of retinal cells, such as age associated macular degeneration, are due at least in part to cellular damage induced by free radicals and oxidative stress. By reducing or depleting neuronal and retinal glutathione, acetaminophen might trigger, accelerate or otherwise worsen these diseases. This hypothesis can best be tested in a large prospective cohort study of acetaminophen use and the risk of these diseases in humans. An acceptable alternative study design would be a population based retrospective cohort study. Although not necessarily predictive of human disease, acetaminophen can also be studied in animal models and with in vitro models of human neurodegenerative and occulodegenerative diseases.