Alzheimer’s: Aspirin may reduce toxic plaque

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.

The protein aggregates in “clumps” that break down the communication between brain cells.

This will trigger the brain’s immune cells, which cause inflammation, eventually leading to the degeneration and death of neurons.

Although the precise cause of Alzheimer’s remains unknown, the “amyloid hypothesis” holds that this accumulation of amyloid is the primary cause.

A consequence that would flow naturally from the theory above is that activating or boosting the brain mechanisms for clearing up cellular waste should slow the progression of the disease.

In fact, some studies have suggested that malfunctioning lysosomes — the “garbage disposals of the cell” — are the reason why amyloid beta builds up in the first place. Other studies point to an association between aspirin use and a lower risk of Alzheimer’s.

New research ties these two pieces of evidence together and reveals that aspirin stimulates the waste-clearing lysosomes and reduces pathological plaque in mice.

Dr. Kalipada Pahan, the Endowed Chair of Neurology and a professor of neurological sciences, biochemistry, and pharmacology at the Rush Medical College in Chicago, IL, led this study.

Low-dose aspirin reduces amyloid plaque

“Understanding how plaques are cleared is important to developing effective drugs that stop the progression of Alzheimer’s disease,” says Dr. Pahan.

He explains that a protein called TFEB plays a key role in regulating the brain’s debris-clearing mechanisms. TFEB is a transcription factor, often “known as a master regulator of lysosomal biogenesis,” or production.

Dr. Pahan and team genetically modified mice so that they displayed Alzheimer’s-like symptoms and brain pathology. They also measured the amount of beta-amyloid that accumulated in the rodents’ brains.

The experiment revealed that aspirin intake upregulated TFEB, which, in turn, stimulated the production of lysosomes. Importantly, “oral administration of low dose of aspirin decreased amyloid plaque pathology in both male and female” mice.

The findings may be beneficial not only for people living with Alzheimer’s disease, but also for the treatment of lysosomal storage disorders, a group of 50 rare conditions with symptoms ranging from mild to severe brain disease.

“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,” says Dr. Pahan.

The research “adds another potential benefit to aspirin’s already established uses for pain relief and for the treatment of cardiovascular diseases,” he continues.

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.”

Dr. Kalipada Pahan

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