A characteristic of Alzheimer’s disease is the alteration of a protein that resides in the brain. The protein, called tau, is present in normal brains and is believed to be responsible for the health of nerve cells.
In the brain cells of people with Alzheimer’s, tau proteins combine into twisted structures known as “neurofibrillary tangles.” The presence of tangles defines the condition as Alzheimer’s.
However, although the tangles confirm Alzheimer’s, their precise role in Alzheimer’s pathology has long been a point of contention among researchers.
New research on the intermediary steps between a single tau protein unit and a neurofibrillary tangle confirms the significance of tau to Alzheimer’s. Scientists now believe the conglomeration of two, three, four, or more tau proteins — known as “oligomers” — are the most toxic entities in Alzheimer’s.
“What we discovered is that there are smaller structures that form before the neurofibrillary tangles, and they are much more toxic than the big structures,” said Rakez Kayed, University of Texas Medical Branch.
“And we established that they were toxic in real human brains, which is important to developing an effective therapy.”
According to Kayed, a key antibody enabled the research team to produce a detailed portrait of tau oligomer behavior in human brain tissue. The anitbody made it possible for researchers to use a variety of analytical tools to compare samples of Alzheimer’s brains with samples of age-matched healthy brains.
“One thing that’s remarkable about this research is that before we developed this antibody, people couldn’t even see tau oligomers in the brain,” Kayed said.
“With the antibody — called T22 — we were able to thoroughly characterize them, and also study them in human brain cells.”
Among the researchers’ most striking findings: in some of the Alzheimer’s brains they examined, tau oligomer levels were as much as four times higher as those found in age-matched control brains.
Other experiments revealed specific biochemical behavior and structures taken on by oligomers, and demonstrated their presence outside neurons — in particular, on the walls of blood vessels.
Investigators believe the discovery will foster renewed studies on Alzheimer’s. “We think this is going to make a big impact scientifically, because it opens up a lot of new areas to study,” Kayed said. “It also relates to our main focus, developing a cure for Alzheimer’s. And I find that very, very exciting.”