Aspirin Intensifies Disposal of Alzheimer's Plaque

Besides relieving pain and reducing the chances of heart attack and stroke, aspirin may also slow the progression of Alzheimer’s disease.  Alzheimer’s disease, a form of dementia that affects 1 in 65 seniors in the United States, is characterized by a toxic buildup of a “sticky” protein fragment called beta-amyloid in the brain.

According to a new study from the Rush University Medical Center, aspirin stimulates lysosomes, tiny garbage-disposal units that clear cellular debris such as unwanted proteins and worn-out organelles – as well as amyloid plaques. Amyloid plaques, clumps of amyloid beta (Aβ) protein, have long been implicated in Alzheimer’s and other neurodegenerative disorders.

Previous studies suggested that aspirin can reduce the risk and prevalence of Alzheimer’s disease. These studies, however, didn’t clarify aspirin’s anti-Alzheimer’s mechanism of action. The new study, which appeared in The Journal of Neuroscience, delineates a mechanism to explain how low-dose aspirin, in a mouse model of Alzheimer’s, succeeded in decreasing cerebral plaque load.

Details of the mechanism appeared in an article entitled “Aspirin Induces Lysosomal Biogenesis and Attenuates Amyloid Plaque Pathology in a Mouse Model of Alzheimer’s Disease via PPARα.” PPARα is peroxisome proliferator-activated receptor α. According to the article, aspirin-activated PPARα upregulates transcription factor EB (TFEB), a master regulator of lysosomal biogenesis. Essentially, TFEB increases lysosomal biogenesis in brain cells.

“Interestingly, aspirin induced the activation of PPARα and stimulated the transcription of Tfeb via PPARα,” the article indicated. “Finally, oral administration of low dose of aspirin decreased amyloid plaque pathology in both male and female 5XFAD mice in PPARα-dependent fashion.”

These findings, the article argued, suggest that low-dose aspirin may be used in lowering storage materials in Alzheimer’s as well as lysosomal storage disorders.

“The results of our study identify a possible new role for one of the most widely used, common, over-the-counter medications in the world,” said Kalipada Pahan, Ph.D., the study’s senior author and lead research investigator, who also is the Floyd A. Davis, M.D., Endowed Chair of Neurology and professor of neurological sciences, biochemistry and pharmacology in Rush Medical College. “Understanding how plaques are cleared is important to developing effective drugs that stop the progression of Alzheimer’s disease.

“This research study adds another potential benefit to aspirin’s already established uses for pain relief and for the treatment of cardiovascular diseases. More research needs to be completed, but the findings of our study have major potential implications for the therapeutic use of aspirin in Alzheimer’s disease and other dementia-related illnesses.”