Researchers said that they may have discovered the molecular-level cause of Alzheimer’s disease.
Scientists at the University of California—Riverside, in recent findings, said that the key to understanding Alzheimer’s may have to do with “tau” proteins that likely caused neurofibrillary tangles—which are found in the brains of Alzheimer’s patients. Previously, researchers have suggested that amyloid plaques, which are a buildup of amyloid peptides, may also be the cause.
Both amyloid plaques and the neurofibrillary tangles are two critical indicators that doctors look for when trying to diagnose Alzheimer’s.
“Roughly 20 percent of people have the plaques, but no signs of dementia,” said UCR Chemistry Professor Ryan Julian in a release. “This makes it seem as though the plaques themselves are not the cause.”
Researchers focused on the different structures a single molecule can manufacture, known as an isomer.
“An isomer is the same molecule with a different three-dimensional orientation than the original. A common example would be hands. Hands are isomers of each other, mirror images but not exact copies. Isomers can actually have a handedness,” Julian said.
The team scanned proteins in brain samples that were donated to their lab, and in brains where there was an accumulation of the tau protein but no Alzheimer’s diagnoses, they found that the “normal” tau had a different-handed form than in individuals who had plaques or tangles, and who were diagnosed with Alzheimer’s. The proteins also survived longer than what is considered normal, the researchers said.
If a protein stays too long—generally more than 48 hours—some amino acids in the proteins convert into the “other-handed” isomer, they noted.
In the news release, Julian said that handedness in isomers is similar to a pair of human hands that mirror one another but are not the same.
Julian noted: “If you try to put a right-handed glove on your left hand, it doesn’t work too well. It’s a similar problem in biology; molecules don’t work the way they’re supposed to after a while because a left-handed glove can actually convert into a right-handed glove that doesn’t fit.”
The human body has a process called autophagy, they noted, which is clears used or defective proteins from cells. When people age, autophagy can slow down, although it isn’t clear why, Julian said, which is what his team is attempting to figure out.
“if a slowdown in autophagy is the underlying cause, things that increase it should have the beneficial, opposite effect,” he said.
