NRI-Impact-Report-2019_WEB

Alzheimer’s disease
Multiple Duncan NRI labs have discovered genes that increase
susceptibility to Alzheimer’s disease and identified targets for
therapeutic intervention:
Published in Cell Reports, August 2019:
A new study sheds light on how the CD2AP gene may enhance
Alzheimer’s disease susceptibility. Researchers discovered that
CD2AP affects neuronal communication by regulating the levels of
key proteins present at neuron terminals (synapses). As a part of this
multi-institutional study led by a team at the Duncan NRI, researchers
examined a collection of more than 800 brain autopsies and found
that low CD2AP levels significantly correlated with abnormal loss of
synaptic proteins, and this relationship was enhanced in the setting
of Alzheimer’s disease.
Published in Cell, August 2019:
A collaborative study with Massachusetts General Hospital at Harvard
Medical School reveals that the ATAXIN-1 gene, which is known to
cause the rare neurodegenerative disease called spinocerebellar
ataxia type 1 (SCA1), also can increase the risk of Alzheimer’s
disease. When a team of researchers—including Drs. Jaehong Suh,
Rudolph Tanzi, and Huda Zoghbi—removed the ATAXIN-1 gene in
mice, they found increased amyloid beta peptides and disruption
of both neuronal connectivity and neurogenesis, which may explain
observations of learning and memory problems.
Published in Cell Reports, October 2019:
A study from the Duncan NRI provides evidence for a new molecular
cause for neurodegeneration in Alzheimer’s disease. By integrating data
from human brain autopsy samples and fruit flies, Dr. Joshua Shulman
revealed a novel mechanistic link between alterations in RNA splicing
and neurodegeneration in Alzheimer’s disease. RNA splicing is one
of the important ways by which organs generate different proteins in
the cells, each of which performs specialized functions. This discovery
shows how aggregates of tau protein within neurons—a key marker
of Alzheimer’s disease—interferes with RNA splicing and presents the
possibility of using RNA splicing as a molecular target for Alzheimer’s
disease and other tau-mediated neurodegenerative conditions.
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