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New Clues To Early Neuron Damage In Alzheimer's Disease

Date:
October 16, 1997
Source:
Columbia University College of Physicians and Surgeons
Summary:
Columbia University College of Physicians & Surgeons scientists have discovered a molecule, called ERAB, that provides an important clue to how early neuron damage may occur in Alzheimer's disease. The findings, published in the Oct. 16, issue of Nature, may lead to a intracellular target for the eventual treatment of the disease.
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NEW YORK, N.Y., Oct. 15, 1997--Columbia University College of Physicians& Surgeons scientists have discovered a molecule, called ERAB, that provides animportant clue to how early neuron damage may occur in Alzheimer's disease. Thefindings, published in the Oct. 16, issue of Nature, may lead to a intracellulartarget for the eventual treatment of the disease.

Alzheimer's disease is a progressive neurodegenerative disorder in whichnerve cells in the brain die. It is the fourth leading cause of death in theUnited States, affecting more than four million people. Scientists have longknown that amyloid-beta peptide, a precursor protein involved in Alzheimer'sdisease, collects in sticky clumps called "neuritic plaques" outside of nervecells in the brain, and eventually kills them. The discovery may allowscientists to develop therapies that inhibit the interaction of ERAB andamyloid-B peptide and protect neurons from damage.

Lead author Dr. Shi Du Yan, assistant professor in the department ofpathology, and senior author Dr. David Stern, professor with joint appointmentsin the departments of physiology and cellular biophysics and surgery, discoveredthat neuronal damage in Alzheimer's disease takes place even before increasedlevels of amyloid-beta peptide accumulate outside of cells.

Since amyloid-beta peptide is produced within cells, scientists lookedfor targets within the cell via which the peptide causes early damage.Researchers identified the first intracellular target of amyloid-beta peptide and named it ERAB.

"This study implicates ERAB as a participant in causing neuronaldysfunction in Alzheimer's disease," says Dr. Yan. The finding contributes to anewly emerging picture of how neuron damage occurs in Alzheimer's disease. Inthe traditional view, large extracellular accumulations of amyloid-beta peptide,as happens in the late stages of Alzheimer's disease, cause non-specificinjuries to neurons. "But the identification of ERAB is one indication that inAlzheimer's disease, the earliest disturbances in neuronal function may occurintracellularly and result from specific interactions of amyloid-beta peptidewith molecular targets," says Dr. Stern. "Identifying such changes at an earlystage may allow therapies to be initiated before neuronal loss and its severeconsequences become manifest."

ERAB is found in a wide range of cells where scientists believe it isinvolved in the metabolism of fatty acids. The CPMC researchers found that whenERAB interacts with amyloid-beta peptide, it increases the toxicity of thepeptide. The researchers also found that blocking the interaction of ERAB andamyloid-beta peptide protects cells from damage."Given the apparent widespread distribution of ERAB throughout the body, thisfinding, while important in its own right -- for pointing toward mechanisms ofamyloid-induced neurodegeneration, also has the potential to contribute to amore complete understanding of vascular dementia," says Dr. Stephen Snyder,Health Science Administrator for the Neuroscience and Neuropsychology of agingprogram at the National Institute on Aging.

The finding may allow scientists to develop therapies that inhibit theinteraction of ERAB and amyloid-B peptide, protecting neurons from damage. Drs.Stern and Yan are now working to identify specific cellular targets ofamyloid-beta peptide, which will help in creating such therapies.

The study's other authors were Xi Chen, Jin fu, Claudio Soto, HuaijieZhu, Futwan Al-Mohanna, Kate Collison, Aiping Zhu, Eric Stern, Takaomi Saido,Masaya Tohyama, Satoshi Ogawa, and Alex Roher.

The study was funded by the National Institute on Aging (NIA), part ofthe National Institutes of Health, and the Columbia University department ofsurgery research fund.

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The above post is reprinted from materials provided by Columbia University College of Physicians and Surgeons. Note: Materials may be edited for content and length.


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Columbia University College of Physicians and Surgeons. "New Clues To Early Neuron Damage In Alzheimer's Disease." ScienceDaily. ScienceDaily, 16 October 1997. <www.sciencedaily.com/releases/1997/10/971016043330.htm>.
Columbia University College of Physicians and Surgeons. (1997, October 16). New Clues To Early Neuron Damage In Alzheimer's Disease. ScienceDaily. Retrieved August 28, 2015 from www.sciencedaily.com/releases/1997/10/971016043330.htm
Columbia University College of Physicians and Surgeons. "New Clues To Early Neuron Damage In Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/1997/10/971016043330.htm (accessed August 28, 2015).

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