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March 11, 2004
Loss of Smell Linked to Key Protein in Alzheimer’s
Disease, New Penn Study Shows
First signal of disease could provide future
test for early stages of neurodegenerative illnesses
(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine have linked
smell loss in mice with excessive levels of a key protein
associated with Alzheimer’s and Parkinson’s
disease. Smell loss is well documented as one of the
early and first clinical signs of such diseases. If
smell function declines as the levels of this protein
increase in brain regions associated with smelling,
the research could validate the use of smell tests for
diagnosing Alzheimer’s disease. Their findings
appear in the March 12th issue of the journal Brain
Research, the commemorative volume 1000.
“The loss of smell - or olfactory dysfunction
- has been known for more than a decade as an early
sign of several neurodegenerative diseases, but we have
never been able to link it to a pathological entity
that is measurable over time,” said Richard
Doty, PhD, Professor and Director of Penn’s
Smell and Taste Center, who is also the team leader
of the study. “By tying decrements in the ability
to smell to the presence of key disease proteins, such
as tau, we may well be able to assess the degree of
progression of selected elements of Alzheimer’s
disease and related disorders by scores on quantitative
smell tests.”
A total of ten mice were evaluated in this experiment
- five mice that were genetically engineered to be a
model for human Alzheimer’s and Parkinson’s
disease, and five normal control mice that do not overexpress
tau proteins. Olfactory dysfunction was evaluated by
measuring the amount of time the mice spent investigating
unfamiliar odors, such as peppermint or vanillin. Unlike
normal mice, those with smell deficits do not spend
much time investigating such odors, and do not show
a preference for “novel” odors over “familiar”
odors.
The results of the Penn study showed that only the control
mice, with no excess of tau proteins, expressed an interest
in new odors, indicating a normal sense of smell. The
mice that had excess in tau protein showed little or
no interest in such odors, implying olfactory dysfunction.
Analysis of brain tissue from the diseased mice confirmed
a link between the olfactory loss and the presence of
excess tau proteins in brain structures important for
smelling. Additionally, the genetically engineered mice
exhibited a significant amount of neurofibrillary tangles,
structures also linked to Alzheimer’s disease.
No test currently exists for the detection of Alzheimer’s
disease. A definitive diagnosis is only confirmed upon
death when the brain tissue becomes available for testing
of the presence of such proteins and other physiological
markers of the disease.
The process for diagnosis before death is less certain
and involves several kinds of tests - for memory, problem
solving, attention and counting - plus review of a patient’s
complete medical history from a primary care physician,
and possibly brain scans and consultations from other
specialists. With several diagnostic tools and criteria,
physicians can make a diagnosis of moderate to severe
stages of Alzheimer's disease with 90 percent accuracy.
However, diagnosis is less certain for the early stages
of the illness.
No explanation exists for what causes the alterations
in smell perception associated with neurodegenerative
disorders. What is known is that key physiological markers
for these illnesses - deposits of neurofibrillary tangles
or amyloid plaques, Lewy bodies or tau and alpha-synuclein
proteins - are commonly found in brain regions associated
with the perception of odors in the bodies of people
who suffer from these illnesses.
“The mice who overexpress tau, a protein associated
with a family of neurological disorders that includes
Alzheimer’s disease and Parkinson’s disease,
have decreased ability to smell,” said Doty. “We
next plan to study the progression of the disease entities
in the brain as it relates to smell dysfunction. These
experiments are part and parcel to better understanding
the physical causes of such neurodegenerative diseases.”
For
a printer friendly version of this release, click
here.
# # #
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is a $2.5 billion enterprise dedicated to the related
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of the University of Pennsylvania School of Medicine
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Penn’s School of Medicine is ranked #2 in the
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