A group of chemicals found in cigarette smoke and car exhaust may increase the risk of developing Alzheimer's disease or accelerate its onset, according to a group of researchers.
The researchers have shown these chemicals, known as type-2 alkenes, are toxic to cells growing in lab dishes, and damage nerve endings in the brains of animals. Researchers say these nerve endings stop working properly in the early stages of Alzheimer's disease .
Other recent studies have shown these chemicals are found in the brains of Alzheimer's patients in regions needed for memory and cognition, and the researchers said type-2 alkenes from the environment could act in concert with the same chemicals occurring naturally in the brain during the development of the disease.
The hypothesis fits with earlier work showing that smoking increases the risk of Alzheimer's disease , said Richard M. LoPachin, a neurochemist at the Montefiore Medical Center in New York, who suggested the hypothesis along with his colleagues.
"Over years and years of smoking and being exposed to type-2 alkenes in the environment," along with the brain's natural production of type-2 alkenes, could be what makes the nerve cells stop working, LoPachin said.
The tips of axons the long, slender appendages of nerve cells are particularly vulnerable to damage, LoPachin said. The proteins in these nerve endings take a long time to be replaced because they are so far away from the main protein-making parts of the cell.
Type-2 alkenes bind to proteins in nerve endings and take them out of commission, LoPachin said, preventing them from functioning properly.
Some of these chemicals are even found in our food, LoPachin said, noting that acrylamide, a type-2 alkene, is present in french fries.
Many researchers support the idea that plaques in the brain , made up of proteins called amyloid-beta peptides play a key role in causing Alzheimer's. LoPachin said his idea may fit with the amyloid hypothesis. Amyloid-beta peptides have been shown to cause a type of damage known as oxidative stress at nerve endings. Oxidative stress is also known to produce certain type-2 alkenes, he said.
However, other researchers say more evidence is needed to show these chemicals cause changes specific to Alzheimer's disease.
"Most of the data would suggest that these are more general toxins, that impact the brain in a more general way," said Ralph Nixon, a professor at New York University's Langone Medical Center, who studies Alzheimer's disease.
"There's no question that they are toxins," Nixon said. "It's just that making that additional leap to say that they are the cause of Alzheimer's disease, or that they accelerate Alzheimer's disease requires evidence that still needs to be acquired," he said.
But if future research continues to implicate type-2 alkenes in Alzheimer's, LoPachin and his colleagues may have found a compound that could combat their toxic effects. The compound, known as 2-ACP, binds to type-2 alkenes so that they cannot damage nerve endings. However,
LoPachin noted, so far they have only studied cells in lab dishes using 2-ACP, and further studies would need to confirm the effect in animals.
The study on 2-ACP will be published in an upcoming issue of the Journal of Neurochemistry.