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Study Links Amyloid Plaques In Alzheimer's Brains To Genes Vital To Normal Memory

Date:
June 27, 2003
Source:
University Of South Florida Health Sciences Center
Summary:
The buildup of Alzheimer's-associated amyloid plaques in the brain dramatically inhibits several genes critical to memory and learning, University of South Florida College of Medicine researchers have found.

Tampa, FL (June 27, 2003) -- The buildup of Alzheimer's-associated amyloid plaques in the brain dramatically inhibits several genes critical to memory and learning, University of South Florida College of Medicine researchers have found.

The strong link between the decreases in select memory genes and amyloid accumulation was observed both in mice genetically engineered to develop memory loss and in the brains of deceased Alzheimer's patients. The results are reported in the June 15 issue of the Journal of Neuroscience published online today.

"Blocking the ability of amyloid to inhibit, or down-regulate, these genes may improve memory in patients with early Alzheimer's disease," said principal investigator David Morgan, PhD, professor of pharmacology and therapeutics and director of the Alzheimer's Disease Research Laboratory at USF.

Many experimental approaches to treating Alzheimer's disease, including the vaccine, try to prevent the further formation of amyloid plaques or remove some of them from the brain. But, Dr. Morgan said, by the time memory loss becomes apparent the toxic plaques are probably accumulating too quickly to eliminate enough amyloid needed to restore normal memory.

"Our study suggests a new approach to treating this neurodegenerative disease that would enhance amyloid-lowering approaches," he said. "For instance, you might give a vaccine or some other immune therapy to reduce the amyloid load and then start the patient on a memory-enhancing drug to block the effect of any remaining amyloid on normal learning and memory."

"This interrogation of the genome reveals new targets for both study and intervention," says D. Stephen Snyder, Ph.D., of the Etiology of Alzheimer's Disease-Cell Biology area of the National Institute on Aging, which funded the research. "This study addresses the important question of what genes related to learning and memory are regulated either up or down by amyloid."

Loss of recent memory is one of the first symptoms of Alzheimer's disease, occurring years before enough nerve cells are choked off to cause disability and death. The USF researchers were trying to determine what triggers this early memory loss if neurons and their connections are still intact.

They used a technique known as microarray analysis to simultaneously screen thousands of genes from brain tissue of mice bred to develop Alzheimer's-associated amyloid plaques. A second more specific technique, quantatitive reverse transcriptase polymerase chain reaction, confirmed the study results.

Six of at least 30 known genes associated with memory and learning were dramatically reduced, or down-regulated, in the mouse model for Alzheimer's disease when compared to the control mice with normal memory. Furthermore, in the mouse model these six genes were signficantly decreased in regions of the brain containing amyloid, the hippocampus and cerebral cortex, but remained unchanged in amyloid-free regions of the brain.

The researchers then compared their findings in the mouse model with an analysis of human Alzheimer's disease tissue from the Brain Donation Program at Sun Health Research Institute in Sun City, AZ.

The same six memory-associated genes reduced in the mousel model for Alzheimer's -- Arc, Zif268, NR2B, GluR1, Homer-1a and Nur77/TR3 -- were also significantly underexpressed in the amyloid-containing regions of brains from deceased Alzheimer's patients. In the the amyloid-free regions of the human brains, the genes again remained unchanged.

Furthermore in the human brains, unlike the mouse brains, all genes related to neural activity were reduced, likely because the human tissue was littered with dead nerve cells characteristic of late-stage Alzheimer's disease, Dr. Morgan said.

The collective evidence strongly suggests that the start of amyloid deposits in the brain selectively reduces expression of a group of genes highly sensitive to amyloid and essential for forming new memories.

"Whether this change results in the neural death leading to Alzheimer's disease remains to be seen," Dr. Morgan said.

In addition to Dr. Morgan, investigators were first author Chad Dickey, PhD, and Marcia Gordon, PhD, both from the USF Alzheimer's Disease Research Laboratory; and Jeanne Loring, PhD; Julia Montgomery, PhD; and P. Scott Eastman, PhD, all of Incyte Genomics Inc. in Palo Alto, CA.


Story Source:

The above story is based on materials provided by University Of South Florida Health Sciences Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of South Florida Health Sciences Center. "Study Links Amyloid Plaques In Alzheimer's Brains To Genes Vital To Normal Memory." ScienceDaily. ScienceDaily, 27 June 2003. <www.sciencedaily.com/releases/2003/06/030626235900.htm>.
University Of South Florida Health Sciences Center. (2003, June 27). Study Links Amyloid Plaques In Alzheimer's Brains To Genes Vital To Normal Memory. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2003/06/030626235900.htm
University Of South Florida Health Sciences Center. "Study Links Amyloid Plaques In Alzheimer's Brains To Genes Vital To Normal Memory." ScienceDaily. www.sciencedaily.com/releases/2003/06/030626235900.htm (accessed September 19, 2014).

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