Study links amyloid plaques in Alzheimer's brains to genes vital to normal memory

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 gene

Contact: Anne DeLotto Baier
University of South Florida Health

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