Dogs and cats in their dotage

Science News, Oct 17, 1998 by Susan Milius

The search for physical signs of aging, or of age-related disorders, in dog brains dates back as far as 1914. In recent years, some of the most-discussed work has come from Brian J. Cummings, Carl W. Cotman, and their colleagues at the University of California, Irvine (UCI). After examining preserved dog brains, the researchers in 1993 described plaques of a nerve-harming protein called beta-amyloid often appearing in old brain tissue. The protein gobs in dogs resemble the denser plaques of beta-amyloid that are characteristic of the brains of Alzheimer's patients. However, dogs fail to develop the second major kind of brain deposit seen in Alzheimer's, knots of material called neurofibrillary tangles.

Even without tangles, plaques may correlate with behavior changes in dogs. Research by Elizabeth Head, also at UCI, and others shows that dogs whose brains hold lots of plaques are more likely to flub certain learning tests. Ability to remember locations declines, as do scores on tests that require dogs to associate a food reward with one stimulus but not another. Also, dogs with more plaques make more mistakes in so-called reversal learning, in which the animal learns that an action will earn a food reward and then must learn to perform the opposite action to get the reward.

Cummings has suggested that these older dogs could be useful for researchers studying the early stages of a human brain sinking into Alzheimer's.

Lary C. Walker of Parke-Davis Pharmaceutical Research in Ann Arbor, Mich., notes that dogs may have been the first animal known to develop brain plaques with age, but researchers have found similar deposits in monkeys and even polar bears. They have also genetically engineered mice that build up brain plaques.

"I hate to throw cold water on these things," Walker says, "but there is no animal that completely models Alzheimer's disease." None of the animals examined seem to develop tangles in their brains. As far as animal behavior goes, "there's nothing that reaches the degree of decline in humans."

However, Walker argues, canine senior citizens can help researchers study another condition inter-twined with Alzheimer's. Beta-amyloid also accumulates within blood vessels in the brain, boosting the risk of strokes. Dogs, he notes, make great laboratory models for this buildup.

So far, no evidence shows one breed more at risk than another for plaque buildup, Ruehl says. Yet researchers aren't ready to dismiss genetics as contributing to cognitive dysfunction. Michael Russell of the University of California, Davis found that laboratory beagles whose brains built up a lot of plaque were likely to have littermates with the same trait. And beagles with cleaner brains had similar littermates.

Cat geriatrics has lagged behind dog studies, but Landsberg presented informal survey results about cats at this year's annual meeting of the American Veterinary Medical Association in Baltimore. He conducted clinical trials of Deprenyl Animal Health's new drug for cognitive dysfunction in dogs and then asked owners of 32 older cats if they had noticed similar declines.