Supplements derived from apple skins, red wine and turmeric might someday help slow the onset and progression of Alzheimer's and related diseases, according to accumulating evidence.
The details are complicated and still a matter of debate. But the scientists involved are basing their strategy on what they say is a new way of thinking about Alzheimer's.
In their view, a group of chemicals called type-2 alkenes, which are widespread in both the environment and the brains of Alzheimer's patients, act as major drivers of the disease. In turn, said chemical neurotoxicologist Richard LoPachin, neutraceuticals of the future could stop these brain-damaging chemicals in their tracks.
Already, LoPachin's group has developed just such a compound that, in Petri dishes at least, sops up type-2 alkenes and protects nerves from harm.
"If you talk to someone else, they may tell you I'm nuts," said LoPachin, of the Montefiore Medical Center in Bronx, New York. "We know that humans are pervasively exposed to type-2 alkenes, but nobody has ever considered the possibility that type-2 alkenes in the environment might be involved in Alzheimer's. It's a new theory of Alzheimer's."
Alzheimer's is a multi-faceted disease and efforts to understand it have followed a variety of paths. One line of research focuses on the endings of nerve cells in the brain, which degenerate as the disease progresses.
When that happens, communication among nuerons breaks down, leading to confusion, forgetfulness and other hallmark symptoms of Alzheimer's.
While scientists disagree about what causes nerve-ending degeneration, studies have clearly shown that the progression of the disease itself produces type-2 alkenes in the brain. Chemicals in this group, such as acrylamide and methylvinyl ketone, also show up in car exhaust, cigarette smoke, industrial settings, even French fries.
Exposure to type-2 alkenes in the environment has already been linked with cancer, heart disease, and other problems. For Alzheimer's patients, LoPachin argues, the double whammy of exposure from both within the brain and from out in the environment could accelerate the onset and progression of the disease.
As evidence, he points to studies showing that Alzheimer's patients have large amounts of type-2 alkenes in their brains. The chemicals appear to selectively target the ends of nerve cells, which are highly vulnerable to damage. And cigarette smoking increases the risk of Alzheimer's by more than 150 percent, possibly because of the type-2 alkenes in tobacco smoke.
If LoPachin is right, then mopping up type-2 alkenes in the brain should help fight Alzheimer's as well as other problems, such as Parkinson's, spinal cord injuries, and strokes. In a new paper in the Journal of Neurochemistry, LoPachin and colleagues report the development of just such an anecdote.
The researchers drew inspiration from a group of well-studied chemicals made by some plants, including resveratrol in grapes, curcumin in turmeric, and phloretin in apple skins. These compounds, which are all similar in chemical structure, have promising characteristics, but the human body does not easily absorb them, and they can be toxic at very high doses.
Instead, the researchers used the structure of these natural plant compounds to develop a new chemical, called 2-ACP.
In their lab studies, 2-ACP latched onto a type-2 alkene called acrolein and prevented the toxin from damaging nerve cells.
Years of testing — first in animals, then people — await the new molecule, LoPachin said. But he thinks the research is an important step in the battle against Alzheimer's.
Other experts are more cautious. Neutralizing type-2 alkenes in the brain will likely be a good strategy for fighting Alzheimer's, said D. Allan Butterfield, a biological chemist at the University of Kentucky, Lexington. And the new study confirms many details that other studies have already showed.
But he disagreed with the argument that type-2 alkenes in the environment are part of the story.
"There's no evidence at all that these cause Alzheimer's," Butterfield said. "I'm an expert on Alzheimer's. I can't claim to say they might not be important in something like cancer. I don't know. But in Alzheimer's, I'm convinced that's not the case."
He also questioned the practicality of a supplement like the kind that LoPachin and colleagues are working on. At this point, he said, the doses in question are far too high to be safe for people.
"If you slowly increase the concentration of molecules like curcumin, you find ever increasing benefits, but at some point, there is a very sharp decline such that there is horrendous harm," Butterfield said. "The therapeutic level and the harmful level may not be that far apart from each other. One would have to be very, very careful."