Acetaminophen: The Case for a Link to Neurodegenerative Diseases

Background

Neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease as well as retinal degenerative diseases, such as age related macular degeneration are all associated with permanent neuronal damage and loss. The causes are for the most part unknown, although for certain diseases genetic factors [1] and advancing age [2, 3] play a role. A Parkinson’s disease like loss of dopaminergic substantia nigra neurons can be triggered in primates by the compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [4]. It has been postulated that environmental toxins may play a role in human neurodegenerative diseases, however to date no such link has been proven. Since the 1970’s, acetaminophen has become increasingly popular as an analgesic and antipyretic throughout the world. Some of this popularity has been driven by marketing although the gastric mucosa toxicity and anti-platelet function activity of aspirin and the classic non-steroidal anti-inflammatory drugs (NSAIDs) have also been a driver. Further, the discovery of the association between aspirin use and Reye’s syndrome in infants and children has tipped the bias towards acetaminophen as a first line anti-pyretic [5]. Also, as the obesity epidemic worsens in the U.S. and other western societies [6], the increasing incidence of osteoarthritis may drive increased analgesic use, including the use of acetaminophen.

Acetaminophen, a relatively small lipophilic molecule, readily crosses the blood/brain barrier where it exerts its antipyretic and analgesic effects.