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Brain Samples Reveal Key Piece of Alzheimer’s Puzzle

Brain Samples Reveal Clue to Cause of Alzheimer's Researchers have discovered a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques associated with this type of dementia.

“There is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in Alzheimer’s disease,” says David L. Brody, M.D., Ph.D., associate professor of neurology at Washington University School of Medicine in St. Louis.

“How this can occur is a tantalizing clinical question. It makes it clear that we don’t understand exactly what causes dementia.”

Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with Alzheimer’s disease, according to Brody. But the presence of the plaques does not always result in impaired thinking and memory, he said.

The new study, published online in Annals of Neurology, still implicates amyloid beta in causing Alzheimer’s dementia, but not necessarily in the form of plaques.

Instead, smaller molecules of amyloid beta dissolved in the brain fluid appear more closely correlated with whether a person develops symptoms of dementia, according to Brody.

Called amyloid beta “oligomers,” they contain more than a single molecule of amyloid beta but not so many that they form a plaque, he explained.

Oligomers floating in brain fluid have long been suspected to have a role in Alzheimer’s disease, but they are difficult to measure. Brody and his colleagues developed a new method to count even small numbers of oligomers in brain fluid.

They examined samples of brain tissue and fluid from 33 deceased elderly subjects between the ages 74 to 107. According to the researchers, 10 subjects were normal with no plaques and no dementia; 14 had plaques, but no dementia; and nine had Alzheimer’s disease, with both plaques and dementia.

The researchers found that cognitively normal patients with plaques and Alzheimer’s patients both had the same amount of plaque, but the Alzheimer’s patients had much higher oligomer levels.

But even oligomer levels did not completely distinguish the two groups, Brody noted. For example, some people with plaques but without dementia still had oligomers, even in similar quantity to some patients with Alzheimer’s disease.

Where the two groups differed completely, according to the researchers, was the ratio of oligomers to plaques. The researchers measured more oligomers per plaque in patients with dementia, and fewer oligomers per plaque in the samples from cognitively normal people.

In people with plaques but no dementia, Brody speculates that the plaques could serve as a buffer, binding with free oligomers and keeping them tied down. And in dementia, perhaps the plaques have exceeded their capacity to capture the oligomers, leaving them free to float in the brain’s fluid, where they can damage or interfere with neurons, he speculated.

Brody cautions that, due to the difficulty in getting samples, oligomer levels have never been measured in living people. Therefore, it’s possible these floating clumps of amyloid beta only form after death. Even so, he says, there is still a clear difference between the two groups.

“The plaques and oligomers appear to be in some kind of equilibrium,” Brody said. “What happens to shift the relationship between the oligomers and plaques? Like much Alzheimer’s research, this study raises more questions than it answers. But it’s an important next piece of the puzzle.”

Source: Washington University School of Medicine

Brain Samples Reveal Key Piece of Alzheimer’s Puzzle

Janice Wood

Janice Wood is a long-time writer and editor who began working at a daily newspaper before graduating from college. She has worked at a variety of newspapers, magazines and websites, covering everything from aviation to finance to healthcare.

APA Reference
Wood, J. (2018). Brain Samples Reveal Key Piece of Alzheimer’s Puzzle. Psych Central. Retrieved on September 27, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 23 Oct 2012)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
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