|Researchers Discover Misfolded Protein Clumps Common
to Dementia, Lou Gehrig’s Disease
Study Provides New Insights into Neurological Disorders
Scientists have identified a misfolded, or incorrectly formed,
protein common to two devastating neurological diseases, frontotemporal
dementia (FTD) and amyotrophic lateral sclerosis (ALS, also known
as Lou Gehrig’s disease), according to a report in the Oct. 6,
2006, issue of Science. The findings suggest that certain
forms of FTD, ALS and possibly other neurological diseases might
share a common pathological process.
Virginia Lee, Ph.D., and John Trojanowski, M.D., Ph.D., of the
University of Pennsylvania, led an international team of scientists
in this discovery. The work was funded by the National Institute
on Aging (NIA), part of the National Institutes of Health (NIH),
and was done at the NIA-funded Alzheimer’s Disease Center at the
University of Pennsylvania School of Medicine Institute on Aging.
“This exciting basic science discovery provides the first molecular
link between a dementia — FTD — and a motor neuron
disease — ALS. It will advance understanding of the pathological
processes of FTD and ALS, and possibly of other neurological disorders,” says
NIA director Richard J. Hodes, M.D. Improved understanding of underlying
disease processes is critically important in pointing researchers
toward the development of therapies for FTD, ALS and other neurodegenerative
diseases, Hodes and the study authors note.
FTD affects the frontal and temporal lobes of the brain. People
with FTD may exhibit uninhibited and socially inappropriate behavior,
changes in personality and, in late stages, loss of memory, motor
skills and speech. After Alzheimer’s disease, it is the most common
cause of dementia in people under age 65.
ALS is a progressive disease of brain and spinal cord motor neurons
that control movement. Over time, walking, eating, speaking and
breathing become more difficult in this fatal disease. Some people
with ALS also have FTD, and some with FTD also develop ALS, suggesting
that common mechanisms might underlie these two diseases.
In certain neurodegenerative diseases, including ALS and some
forms of FTD, scientists have identified clumps of protein — or
inclusion bodies — that accumulate in brain cells and neurons.
However, understanding why they form and what they contain has
been elusive. Lee and Trojanowski have long sought to solve that
Following years of research, they have now identified TDP-43 as
a constituent part of the clumps that form in ALS and in the most
common form of FTD. Although its precise role is not well understood,
TDP-43 is involved in the complex process of transcribing and regulating
genetic information in the nucleus of the cell.
“There is much more to learn about how this nuclear protein is
clumped in the cytoplasm of cells and about the mechanism by which
it is implicated in two distinctly different diseases,” says Stephen
Snyder, Ph.D., program director, etiology of Alzheimer’s disease,
NIA Neuroscience and Neuropsychology of Aging Program. “It is possible
that the TDP-43 protein will be a key to a more complete understanding
of both FTD and ALS.”
NIA leads the federal effort supporting and conducting research
on aging and the medical, social and behavioral issues of older people,
including Alzheimer’s disease and age-related cognitive decline.
For information on dementia and aging, please visit the NIA’s Alzheimer’s
Disease Education and Referral (ADEAR) Center at www.nia.nih.gov/alzheimers,
or call 1-800-438-4380. For more general information on research
and aging, go to www.nia.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.