Clue to Alzheimer’s cause found in brain samples

David Brody and colleagues identify ratio of amyloid beta oligomers to plaques as a marker for dementia Read More

From the WUSTL Newsroom

Researchers at Washington University School of Medicine in St. Louis have found a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques that characterize 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, MD, PhD, associate professor of neurology. “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 simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary — but not sufficient — to cause Alzheimer’s dementia.

Annals of Neurology - The top two brain samples are from normal individuals – no amyloid beta plaque and no dementia. The middle samples are from subjects who have plaque but no dementia. The bottom samples are from subjects who have Alzheimer’s disease — they have both plaque and dementia. Scientists have long wondered why only some patients with plaques develop Alzheimer’s. For the first time, David Brody, MD, PhD, and his colleagues have measured more dissolved amyloid beta oligomers per plaque in patients with Alzheimer’s dementia.

The new study, available 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. Called amyloid beta “oligomers,” they contain more than a single molecule of amyloid beta but not so many that they form a plaque.

Oligomers floating in brain fluid have long been suspected to have a role in Alzheimer’s disease. But they are difficult to measure. Most methods only detect their presence or absence, or very large quantities. Brody and his colleagues developed a sensitive method to count even small numbers of oligomers in brain fluid and used it to compare amounts in their samples.

The researchers examined samples of brain tissue and fluid from 33 deceased elderly subjects (ages 74 to 107). Ten subjects were normal — no plaques and no dementia. Fourteen had plaques, but no dementia. And nine had a diagnosis of Alzheimer’s disease — both plaques and dementia.

They 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. 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 Brody and his colleagues, was the ratio of oligomers to plaques. They measured more oligomers per plaque in patients with dementia, and fewer oligomers per plaque in the samples from cognitively normal people.

For more from Julia Evangelou Strait of the WUSTL Newsroom, click here.

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Posted on October 24, 2012
Posted in: Axon Injury & Repair, HPAN, Neurodegeneration, News Authors: , , , ,