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The focus of Dr. Albers’ laboratory is to gain a mechanistic
understanding of early pathogenic processes of neurodegenerative
diseases that are modifiable or reversible. Using mouse genetics, his
lab has specifically tailored olfactory neurons to express disease
genes associated with Alzheimer’s disease in a reversible manner, such
that the disease gene can be turned off by feeding the mice a low-dose
antibiotic. Patients with Alzheimer’s disease and Parkinson’s disease
suffer olfactory deficits early in the course of their disease,
pointing to a particular susceptibility of this neural circuit to the
pathogenesis of these diseases, and making the olfactory system a
logical starting point. Moreover, the olfactory neural circuit is one
of the best-understood neural circuits in the mammalian brain.
Characterization of this mouse model has uncovered a novel action of
an Alzheimer’s disease gene – expression of this gene in less than 1%
of the primary olfactory neurons is sufficient to cause olfactory
deficits in behavioral assays. Reversal of the disease gene expression
affects a complete recovery of the behavioral deficit in adult mice.
The generous support from the Rappaport Family Fund afforded Dr.
Albers’ team the opportunity to learn that olfactory neurons are dying
at an accelerated rate when the disease gene is expressed. This is the
first mouse neuron population shown to be susceptible to this disease
gene. This advance has generated exciting studies that delve into the
molecular mechanisms leading to accelerated neuronal death and to
develop a system to screen for molecules that interfere with this
neurodegenerative process. Insights gained from these studies may
contribute to the development of an effective therapy for these
devastating diseases. The funds provided by the Rappaport Family
helped support investigator salaries and defrayed costs associated
with laboratory work, ultimately facilitating this important research.
Dr. Albers’ findings will be published as well as presented at two
international meetings.
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