When scientists talk about the cause of Alzheimer’s disease, they tend to refer to the accumulation of proteins that clog and kill brain cells.
It is the apparent mechanisms that shrink the brain and lead to a progressive dementia that deprives a person of who they once were.
A new study claims that the real cause of Alzheimer’s disease is a slowdown in the brain’s ability to purify itself at the cellular level.
Researchers at the University of California (Riverside) say that it is this error in the cleaning process – known as autophagy – that is the real cause of the brain filling up with dirt.
There is already research in play to find a drug that can restore this cleansing process to full effectiveness – and ultimately can help prevent the disease.
Some of these drug treatments include existing treatments for heart disease. If these prove to be effective in purifying brain cells, the regulatory process of approval will be significantly accelerated.
Two kinds of plaques
The only way to diagnose Alzheimer’s disease with certainty is an autopsy, in which the brain is examined for amyloid plaques and neurofibrillary tangles.
Plaques are collections of misfolded proteins that form in the spaces between nerve cells and disrupt brain messages. Tangles largely consist of a protein called tau.
However, not everyone with these plaques develops Alzheimer’s.
“About 20 percent of people have plaques but no signs of dementia,” UCR chemistry professor Ryan Julian said in a prepared statement.
“This makes it seem as if the plates themselves are not the cause.”
So what happens?
Professor Julian and colleagues discovered “an important but difficult to detect difference in the form of tau (there) made it possible for researchers to distinguish between people who did not express any outward signs of dementia from those who did”.
It all came down to a single molecule and the different shapes it can take. These different forms of the same molecule are called isomers.
“An isomer is the same molecule with a different three-dimensional orientation than the original,” said Professor Julian.
He compares isomers with our hands: mirror images of each other, but not exact copies.
“Isomers can actually have a ‘handedness,'” he said.
The amino acids that make up proteins can be either right-handed or left-handed isomers. Usually, “proteins in living things are made of all left-handed amino acids”.
When the researchers scanned all the proteins in donated brain samples, they found that those with brain building but no dementia had normal left-handed tau, while a second-hand form of tau was found in those who developed plaques or tangles as well as dementia.
How does this happen?
Professor Julian said that most proteins in the body have a half-life of less than 48 hours. This means that they remain stable (in their left-hand form) for about a day.
Normally, the purification process would eat up these obsolete proteins and dispose of them. If the purification process fails, certain amino acids can convert the left-handed protein into a second-hand isomer.
“If you try to put a right-handed glove on your left hand, it does not work so well. It is a similar problem in biology; molecules do not work as they should after a while because a left-handed glove can actually be transformed into a right-handed glove that does not fit, ”said Professor Julian.
It is this shift from left-handedness to right-handedness that makes tau proteins problematic.
The autophagic cleansing process is generally slowed down in people over 65 years of age. Researchers plan to investigate why this happens.
Autophagy can be induced by fasting. When cells lack proteins from a person’s diet, they fill the void by reusing proteins already present in cells. Exercise also increases autophagy.