A Nose for Alzheimer's?

Research with smell-impaired mice may lead to early detection test

FRIDAY, March 12, 2004 (HealthDayNews) -- Mice left unimpressed by "meadow fresh," "golden forest" and other sweet aromas are helping scientists sniff out a test to diagnose Alzheimer's disease in its earliest stages.

According to researchers, the sense of smell is one of the first casualties of the disease as it begins its cell-by-cell assault on the human brain. A smell-based early detection test might let patients be treated earlier and more effectively, they say.

"The majority of both Parkinson's and Alzheimer's patients show a demonstrable smell loss very early in the disease process, and in some cases this probably precedes clinical signs," explains Richard L. Doty, director of the Smell and Taste Center at the University of Pennsylvania Medical Center in Philadelphia.

The study appears in the March 12 issue of Brain Research.

The Alzheimer's Association estimates that half of U.S. adults 85 years of age and over now suffer from the disease. Dr. Sam Gandy, vice chairman of the association's National Scientific Advisory Council, says the problem will only worsen with time.

"As the baby boom ages and as the population expands, the number of patients is going to rise dramatically, to the point that the community can't afford it economically," he says.

There is no cure for Alzheimer's, which is characterized on the cellular level by the buildup around brain cells of neurofiber "tangles" and beta-amyloid protein plaque deposits.

Scientists peering closely at Alzheimer's tangles typically see clusters of another brain protein called tau. In their study, Doty and his team bred a team of mice genetically engineered to overproduce tau, to help determine if tau might play a role in the early destruction of the smell sense.

To see just how well the mice could smell, the researchers compared the reactions of mice overproducing tau and normal mice to resin strips perfumed with odors such as "golden forest," "meadow forest" and "vanilla orange spice."

The result? "Mice that overexpress [overproduce] this [tau] protein have difficulty smelling," Doty says. While normal mice sniffed curiously at the odiferous strips, tau-expressing mice nosed about as usual, unperturbed.

The study suggests tau does play a role in the olfactory impairment seen in neurodegenerative illnesses such as Alzheimer's. In fact, when scientists examined the brain tissue of the tau-expressing mice, they spotted signs of degeneration in exactly those brain structures most important to the sense of smell.

However, while a smell-based early detection test would be ideal, "we're not there yet," Gandy cautions. Tau is overproduced in diseases other than Alzheimer's, "so although the smell abnormality might flag that there was a brain problem, it wouldn't necessarily be specific to Alzheimer's," he says.

Doty agrees that smell impairment in old age doesn't necessarily point to brain disease, either. "Over the age of 80 about three out of four people can't smell very well," he notes, "and between 65 and 80 years of age about half the population has a significant smell loss."

Still, any test that could spot Alzheimer's early would be a boon to both research and clinical practice. According to Gandy, who is also director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia, it's important "to identify patients or subjects that are developing early Alzheimer's as soon as possible so they could be subjects for [new] medications."

Those medications "may have only a small window early in the disease to be beneficial," he adds. "If they are given very late they might not help at all."

And although there is no cure for Alzheimer's, drugs such as cholinesterase inhibitors do appear to slow the illness down. Gandy estimates that, if given early enough, "they seem to turn the clock back by about six months -- but the clock keeps ticking. Still, if it's your grandfather and it gives him one more day of recognition of who you are, that could be meaningful."

In the meantime, Doty's team is digging deeper into connections between smell loss and Alzheimer's. They point out that the olfactory system "is a direct route into the brain," bypassing the blood-brain barrier that makes the delivery of drugs to the brain so difficult. Nasal administration of drugs "may be a way to administer certain drugs that don't readily pass the blood-brain barrier," Doty explains, "so that's another angle we're pursuing."

More information

For more information on Alzheimer's, visit the Alzheimer's Association or the Alzheimer's Disease Education and Referral Center.

SOURCES: Richard L. Doty, Ph.D., director, Smell and Taste Center, University of Pennsylvania Medical Center, Philadelphia; Sam Gandy, M.D., vice chairman, National Scientific Advisory Council of the Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; March 12, 2004, Brain Research
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