Nature Medicine study: Onset of Alzheimer's damage accelerated in mice with two genetic defects

Story Source: David Morgan, PhD, (813) 974-3949

Media Contacts: Anne DeLotto Baier or Michael Hoad, (813) 974-3300

Nature Medicine study: Onset of Alzheimer's damage accelerated in mice with two genetic defects

TAMPA, Fla. (13 January 1998) -- Mice with two of the three mutant genes known to cause Alzheimer's disease in humans develop pathological signs of the disease at an accelerated rate, according to a study on the January cover of the journal Nature Medicine.

The joint study by researchers at the University of South Florida, Mayo Clinic in Jacksonville and the University of Minnesota produced an animal model for Alzheimer's that can more rapidly test drugs with potential to slow or prevent the disease.

"This is the Speedy Gonzalez of Alzheimer's mice," said David Morgan, PhD, director of the Alzheimer's Research Laboratory in USF's Department of Pharmacology and a principal investigator for the study. "We can speed up the drug screening process because the mice with two mutant genes develop Alzheimer's-like pathology at an earlier age, two to three times quicker, than mice with just one defective gene."

In the last few years scientists have discovered that early-onset Alzheimer's is caused by mutations in at least three genes --" the beta amyloid precursor protein, the presenilin 1 gene and the presenilin 2 gene.

The USF researchers crossed mice carrying the amyloid mutation with mice carrying the presenilin 1 mutation, and looked at their brains.

The offspring that inherited both mutations, called doubly transgenic mice, had as many deposits of beta amyloid protein in their brains at age four months as did 9-month-old mice carrying the single beta amyloid mutation. At 6 months old, the doubly transgenic mice exhibited the same severity of Alzheimer's-like pathology as 15-month-old mice with the single mutation.

The study demonstrates that both mutations, amyloid and presenilin 1, have identical biochemical effects, Dr. Morgan said. They increase production of beta amyloid, which accumulates in brain lesions called plaques, a hallmark of Alzheimer's.

"This is additional evidence that excess amyloid is a key event in Alzheimer's pathology," Dr. Morgan said.

The USF research was supported by an endowment from Dorothy Benjamin.

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