Loss of Smell May Be Early Alzheimer's Sign
Loss of Smell May Be Early Alzheimer's Sign
HealthSCOUT - March 12, 2004
Mice left unimpressed by "meadow
fresh," "golden forest" and other sweet
aromas are helping scientists sniff out a test to
diagnose Alzheimers disease in its earliest
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 Parkinsons and Alzheimers
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 Alzheimers 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 associations 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 cant afford
it economically," he says.
There is no cure for Alzheimers, 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 Alzheimers 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 Alzheimers. 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, "were not there yet,"
Gandy cautions. Tau is overproduced in diseases other
than Alzheimers, "so although the smell
abnormality might flag that there was a brain problem,
it wouldnt necessarily be specific to Alzheimers,"
Doty agrees that smell impairment in old age doesnt
necessarily point to brain disease, either. "Over
the age of 80 about three out of four people cant
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 Alzheimers 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, its important "to identify
patients or subjects that are developing early Alzheimers
as soon as possible so they could be subjects for
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
And although there is no cure for Alzheimers,
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 its your grandfather and it gives
him one more day of recognition of who you are, that
could be meaningful."
In the meantime, Dotys team is digging deeper
into connections between smell loss and Alzheimers.
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 dont readily pass the blood-brain barrier,"
Doty explains, "so thats another angle
For more information on Alzheimers, visit the
Alzheimers Association or the Alzheimers
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 Alzheimers
Association, and director, Farber Institute for Neurosciences,
Thomas Jefferson University, Philadelphia; March 12,
2004, Brain Research~ENTH~~ALZH~~AGNG~
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