Beagles, Dalmatian Point Way in Alzheimer’s...

For much of her life, Sadie had it all: good health, a fine home, a family that adored her. But with old age came senility, robbing her, bit by bit, of her personality.

Once known for her hearty appetite, she picked at her food, sometimes wandering off in the middle of a meal. She began getting lost in the only home she’d ever known. A lifelong extrovert, she sat for hours staring at the wall.

Test after test came back normal. But the signs were all there: memory loss, confusion, inappropriate outbursts. The doctors were quite certain. They’d seen it before.

Had Sadie been human, she might have lived out her days in a nursing home, or been cared for at home by round-the-clock nurses or aides.

But Sadie was a dog, a 17-year-old Dalmatian, so her life ended quickly and mercifully with a lethal injection.

Her story, however, goes on.

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Sadie’s family donated her body to the University of California at Davis, where researchers examined her aged brain and found something remarkable. Buried within the tissue were protein deposits identical to those found in the brains of human Alzheimer’s patients.

Alzheimer’s disease is a progressive brain disorder that impairs memory, thinking and behavior in 4 million Americans. No cause or cure has been found.

Scientists have long known that aging primates--monkeys, bears, dogs--can develop the amyloid plaques and neurofibrillary tangles that are the hallmarks of Alzheimer’s disease.

What they don’t know is whether these neurological signs are the animal equivalent of Alzheimer’s or simply the more general signature of an aging brain.

The answer may rest in a locked kennel at UC Davis, where 40 aging beagles pass their days playing with toys and with each other. Their primary job: to grow old.

As they age, protein deposits form in their brains that are remarkably similar in size, structure and location to those found in humans with Alzheimer’s.

Periodically, the beagles go swimming in a huge above-ground pool. The surface is covered with colored beads. Hidden beneath the beads is a submerged platform the dogs have been previously shown.

The time it takes them to find the platform gives clues as to their memory ability. The tests are repeated months later.

Michael J. Russell, head of the Canine Aging Project and an assistant professor of anesthesiology and otolaryngology, says the results so far have been intriguing. “In the first test, the old dogs learned faster, but their memory was shot. When we retested 19 dogs a year later, the young dogs did better. The old dogs forgot where the island was.”

That’s significant because inability to recall new events is a primary symptom of Alzheimer’s in humans. “People with Alzheimer’s will sit and tell you what happened 20 years ago. But one reason the illness is so upsetting is that it’s very common for a relative to come in and a patient to say, ‘You’re not my daughter.’ The patient is remembering a much younger child.”

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The Canine Aging Project, funded by the National Institutes of Health, started a year and a half ago. Russell had just put his own mother in a nursing home. At the time, she was thought to have Alzheimer’s disease, although doctors have since attributed her dementia to a series of small strokes.

For animals as well as for humans, Alzheimer’s can’t be definitively diagnosed without an autopsy. So far, of the dogs in Russell’s study, only those with painful or terminal illnesses have been put to sleep. The rest live out their natural life spans, typically about 16 years.

As they die, the dogs’ brains are examined for plaques. The findings are then checked against the animals’ performance in the water maze, for evidence of a connection between neurological signs of disease and memory loss.

So far, only eight dogs have died. But researchers have examined archived tissue from more than 150 others that died at university clinics or that were used in previous life-span studies.

Several patterns have emerged. Whether a dog develops amyloid plaques depends on which litter it came from, suggesting some prenatal influence. “We also think there’s a relationship between breed and heredity,” Russell said.

None of the dogs has developed plaques prior to age 10. That’s also the age when other serious illnesses start to appear, according to clinical records of more than a thousand dogs kept by university veterinarian Dr. Russell White.

“Something happens at age 10 that correlates with other disease processes,” Russell said. “There is a mechanism that allows these events to occur, some threshold or trigger event. I don’t know what it is.”

The length of a dog’s life may also play a role. Big dogs, such as Great Danes and Saint Bernards, have shorter life spans than small dogs, such as poodles and beagles. They also are far less likely to develop plaques.

Despite such differences, “it’s clearly an animal that develops an age-related pathology that resembles Alzheimer’s,” said Jim Geddes, an assistant professor of anatomy and neurobiology at the University of Kentucky’s Sanders Brown Center on Aging.

In addition to shedding new light on Alzheimer’s disease in humans, Russell hopes his study will lead to new treatments that will extend the lives of dogs, particularly service dogs.

The search for an animal model for Alzheimer’s has been under way since shortly after the disease was first described in 1907. Without one, “you’ve got to make some big jumps from the test tube to the human being,” said Peter Davies, a researcher at the Albert Einstein College of Medicine in New York City.

“A good animal model would be enormously valuable. For those of us involved in attempts to devise new strategies for treating Alzheimer’s, one of the great hurdles has been that there’s no animal on which to test new compounds we think might be effective.”

The search has taken on new urgency in light of an aging population. Alzheimer’s disease can affect people in their 40s and 50s, but most of its victims are older.

Studies have shown that the incidence of Alzheimer’s, just 3% at age 65, soars to 45% at age 85. The number of Americans 85 and over is the fastest-growing segment of the population, expected to more than double over the next 25 years. There are now 3.4 million people in this age group. The U.S. Census Bureau projects that by 2020, there will be nearly 7 million.

“We’ve been successful at making people live longer,” Russell said. “As baby boomers approach old age, there will be a huge social and economic drain. The numbers will equal the incidence of AIDS in some African villages.”

The average nursing home stay for a patient with Alzheimer’s is five to seven years, Russell said. The average annual cost per patient: $213,732, according to one recent study.

“The most common cause of death for people with Alzheimer’s is pneumonia,” Russell said. “They die as a result of being bedridden and immobile. You can lose almost all of the cortical layer of your brain and survive. But people can’t stay bedridden for long.”

While no one knows what causes Alzheimer’s, some scientists believe the disease begins when beta-amyloid, a protein sometimes found in healthy brains, inexplicably begins to accumulate into deposits or plaques. The plaques then convert to a toxic--”neuritic”--form that ultimately destroys brain cells.

Other scientists believe amyloid is a byproduct of another disease process that has yet to be discovered.

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Researchers are using genetic engineering and other techniques to try to develop a rat with Alzheimer’s. But even if they succeed, without knowing what causes the disease, they may have no way of knowing whether they’ve re-created the illness or merely mimicked its symptoms, Russell said.

At the same time, he said, 40 lab rats cost just a couple hundred dollars to maintain, compared to $98,000 for 40 dogs. There’s also huge savings in the amount of experimental compounds needed for testing on rats as opposed to dogs.

But rats live just three years, which may not be long enough to develop plaques. “For certain treatments dealing with aging, you need a species with a midlife span,” Russell said. “Dogs get many conditions that are slow developing, like arthritis and heart disease. Here we’ve got a species that lives long enough to be examinable.”

Dogs are also readily available. The American Humane Assn. estimates that 6.3 million dogs were euthanized in 1992. “The question is,” Russell said, “are we going to use that tissue or continue to burn it or bury it?”

Dogs also live with people and share the same conditions, which could provide additional clues with regard to environmental factors implicated in Alzheimer’s.

Dogs raised in rural Poland were found to have fewer senile plaques than those raised in more polluted industrial and urban areas. Russell says the strictly controlled conditions under which his dogs have been raised could explain why they have fewer senile plaques than dogs previously studied.

The discovery of amyloid in dogs dates back to 1912, but nobody paid much attention. Russell blames the difficulty of acquiring enough old dogs, along with the fact that not all breeds develop plaques. “And, socially, we’re all a little uncomfortable--myself included--that it happens to be dogs. If it were sheep or pigs, it would be different.”

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The UC beagles are the legacy of a now-defunct U.S. Department of Energy study that measured the effects of radiation on dogs. These animals were descendants of the control group, the group not exposed to radiation.

“Visitors welcome,” reads the sign posted outside their kennel. The barking begins the minute Russell turns his key in the lock.

They have lived their whole lives on this campus, as have seven or eight generations of beagles before them. Everything reasonable is done to prolong their lives. They’re examined four times a year and fed a special diet developed by university scientists.

Equal attention is paid to their mental health. Though their contact with humans is limited, the dogs have ready access to each other. They’re given toys to play with and bones to chew.

But they are not pets. Pick one up and it looks at you curiously, enjoying the attention but unsure what to make of it. Pet it and its tail will not wag. It will not lick your face, only sniff at you gently.

These are lab animals with a job to do, albeit one that comes naturally. And although researchers have yet to sacrifice any of these animals, they are resigned to doing so should they deem it necessary.

The fight against Alzheimer’s disease “is a war,” Russell said. “You send soldiers to war, and some of them die.”