Nasal NSAIDs for Alzheimer's Disease

Abstract

Alzheimer’s disease may result from low-grade inflammation of the brain, and the characteristic amyloid β may be a protective response. Epidemiological observation indicates that long-term oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to patients having rheumatoid arthritis results in reduced risk and delayed onset of Alzheimer's disease. However, oral ibuprofen, flurbiprofen, and other NSAIDs are not an effective treatment. The NSAIDs may work as an Alzheimer’s preventive but not a treatment because the oral dose to the brain is too small, 1% to 2% of the total plasma concentration. The NSAID brain dose could be significantly increased by delivering the drug intranasally. Flurbiprofen would be preferable to ibuprofen because flurbiprofen has 12½ times the potency of ibuprofen. The smaller nasal dose of flurbiprofen than ibuprofen could significantly increase patient compliance. Alzheimer’s disease starts in the entorhinal cortex, which is closely connected to the olfactory nerves, and spreads anatomically in a defined pattern. Therefore, a nasal NSAID would readily reach the region of the brain where it is most likely to be therapeutic.