Discovery Sheds Light on Why Alzheimer's Drugs Rarely Help

Article ID: 604958

Released: 1-Jul-2013 6:00 AM EDT

Source Newsroom: University of California, Los Angeles (UCLA), Health Sciences

  • Credit: UCLA/Guo lab

    Molecular structures of amyloid oligomers and amyloid fibers.

  • Credit: UCLA

    Lead author Zhefeng Guo, Ph.D., assistant professor of neurology at the David Geffen School of Medicine at UCLA and a member of UCLA’s Brain Research Institute and Molecular Biology Institute.

Newswise —
BACKGROUND
The Alzheimer’s Association projects that the number of people living with Alzheimer’s disease will soar from 5 million to 13.8 million by 2050 unless scientists develop new ways to stop the disease. Current medications do not treat Alzheimer’s or stop it from progressing; they only temporarily lessen symptoms, such as memory loss and confusion.

Current Alzheimer’s drugs aim to reduce the amyloid plaques—sticky deposits that build up in the brain--that are a visual trademark of the disease. The plaques are made of long fibers of a protein called Amyloid β, or Aβ. Recent studies, however, suggest that the real culprit behind Alzheimer’s may be small Aβ clumps called oligomers that appear in the brain years before plaques develop.

FINDINGS
In unraveling oligomers’ molecular structure, UCLA scientists discovered that Aβ has a vastly different organization in oligomers than in amyloid plaques. Their finding could shed light on why Alzheimer’s drugs designed to seek out amyloid plaques produce zero effect on oligomers.

IMPACT
The UCLA study suggests that recent experimental Alzheimer’s drugs failed in clinical trials because they zero in on plaques and do not work on oligomers. Future studies on oligomers will help speed the development of new drugs specifically aiming at Aβ oligomers.

AUTHORS
Zhefeng Guo, an assistant professor of neurology at the David Geffen School of Medicine at UCLA and a member of UCLA’s Brain Research Institute and Molecular Biology Institute, is available for interviews.

JOURNAL
The study was published as Paper of the Week in the June 28 issue of the peer-reviewed Journal of Biological Chemistry.

GRAPHICS
Images of Aβ oligomers and Aβ fibers are available upon request.

FUNDING
The research was supported by the Alzheimer’s Association and American Health Assistance Foundation.


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