Mouse models for Alzheimer’s have never been able to simulate anything comparable to the last stages of the disease. “Plaque-forming mice do not show extensive nerve-cell death,” Gandy says. “It’s nothing like human Alzheimer’s.” But the research group has good reason to believe that their work in pigs will be more successful than the studies in mice. Research indicates that pigs’ nerve cells may possess the biochemical machinery needed to trigger the disease, Jørgensen says. The scientists will use computerized axial tomography and positron-emission tomography (PET) scanners—the same devices that help diagnose Alzheimer’s in humans—to detect the two destructive proteins, beta-amyloid and tau, in early stages. To find beta-amyloid, for instance, the scientists can inject a chemical substance into the bloodstream that attaches to the protein deposits in the brain. If amyloid clumps are present, the substance will accumulate there and be detectable on PET scans. In the later stages of the disease, researchers will be able to follow the progressive death of neurons in the brain using the scanners.
The technology will allow researchers to study for the first time the long-term effects of the disease. “Because the cloned pigs are genetically identical, we expect the pathological changes we find in one pig to be present in the others,” Jørgensen says. This will enable researchers to correlate pathological- disease development with changes in behavior.
One very early behavioral symptom the researchers will look for is a diminished sense of smell. They will also test for a loss of memory and spatial recognition by placing the pigs in a room with four compartments, one of which contains a reward. Healthy pigs quickly learn which compartment contains the reward and go right to it. The pigs with Alzheimer’s, however, will probably have a harder time remembering which compartment holds the reward.
To further test memory, the pigs will be put in a room with two toys. The following day, one of the two toys will be replaced. Healthy pigs spend more time examining new objects, but once the diseased pigs’ memories begin to diminish, it’s expected that they will spend the same amount of time sniffing both the old and new toys.single page
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