Some epidemiological studies have showed that people who smoke tend to have lower incidences of Parkinson's disease and Alzheimer's disease; this has been widely attributed to nicotine. However, nicotine's harmful effects make it a poor drug candidate.
Cotinine, a byproduct of nicotine metabolism, is nontoxic and longer lasting than nicotine.
In the study, genetically engineered 2-month-old mice were given cotinine daily for five months. When tested, those treated with cotinine performed at the same level as normal mice on spatial memory tests, and showed a 26% reduction in deposits of amyloid plaques, compared to the genetically engineered mice who had not received the treatment. Cotinine also inhibited the accumulation of the amyloid peptide oligomers, and stimulated the signaling factor Akt, which promotes the survival of neurons and enhances attention and memory.
The researchers are hoping to carry out a pilot clinical trial to investigate cotinine's effectiveness in preventing progression to Alzheimer's dementia in patients with mild cognitive impairment.
Echeverria, V. et al. In press. Cotinine Reduces Amyloid-β Aggregation and Improves Memory in Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 24 (4).