New Light on how ibuprofen protects against Alzheimer’s disease

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The discovery that ibuprofen and a few other non-steroid anti-inflammatory drugs (NSAIDS) reduced the risk of developing Alzheimer’s disease was a major breakthrough. Scientists assumed that this risk reduction was due to the anti-inflammatory action of ibuprofen, chiefly its inhibition of the enzymes called cyclooxygenases (COX), known to be involved in the inflammatory response. But a new study done jointly at the University of California, San Diego School of Medicine and the Mayo Clinic in Jacksonville, Florida, suggests that the mechanism may involve ibuprofen’s ability to reduce the levels of a protein called amyloid-beta 42. Amyloid-beta 42 is involved in forming deposits of harmful plaque in the neurons. The accumulation of this plaque increases the levels of free radicals, impairs neural cell function, and eventually induces cell death.

Using animal and in vitro studies, Dr. Edward Koo, a neurologist at the University of California, San Diego, and his colleagues discovered that certain NSAIDS such as ibuprofen help protect against the development of Alzheimer’s disease by decreasing the levels of amyloid-beta 42 rather than by inhibiting COX enzymes. Indomethacin and sulindac were also effective. These NSAIDS were able to reduce amyloid-beta 42 by 50% to 80%–but only when high doses were used, such as the equivalent of 16 Advil tablets per day. Aspirin did not affect the levels of amyloid-beta 42. Naproxen and celeloxib (Celebrex), a selective COX-2 inhibitor, were likewise ineffective.

A separate in-vitro experiment using cells genetically modified to lack the COX enzymes showed that the lowering of amyloid-beta 42 levels by certain NSAIDS did not depend on inhibiting COX.

Because in some people NSAIDS can have serious side effects including ulcers, Koo has stated that we need to seek new drugs targeting amyloid-beta 42. Such drugs would be effective at reducing the amount of amyloid-beta 42, but would have no COX inhibiting activity. Do note, however, that previous studies have shown that taking as little as four Advil tablets (800 mg of ibuprofen) per day reduces the risk of contracting Alzheimer’s without serious side effects. In fact, in one study, anit-inflammatory drugs slashed the incidence of Alzheimer’s by 75%. To learn more refer back to “Ibuprofen—Over-The-Counter Drug Is Treatment For Alzheimer’s”