Protein found in Alzheimer's disease
brain plaques also found in the eyes of children with Down syndrome
A team of researchers has discovered that the protein
that forms plaques in the brain in Alzheimer's disease also accumulates in the
eyes of people with Down syndrome. The new findings in Down syndrome show that
the toxic protein, known as amyloid-β, that causes Alzheimer's pathology in the
brain also leads to distinctive cataracts in the eyes. The discovery is leading
the researchers to develop an innovative eye test for early detection of Alzheimer's
pathology in both disorders.
The research, led by Lee E. Goldstein, M.D., Ph.D., associate
professor at Boston University School of Medicine and the Boston University Alzheimer's
Disease Center, and Juliet A. Moncaster, Ph.D., associate director of the Molecular
Aging & Development Laboratory, also at Boston University, was presented at
the annual meeting of the Association for Research in Vision and Ophthalmology
in Fort Lauderdale, Florida and reported in the May 20 issue of PLoS One. The
research included investigators at the Brigham & Women's Hospital; Massachusetts
Eye and Ear Infirmary; Massachusetts General Hospital; Harvard Medical School;
Rush University Medical Center; Children's Hospital Boston, and the University
of Washington, Seattle.
"People with Down syndrome develop symptoms of Alzheimer's-type
dementia often by the age of 30," said Goldstein, senior corresponding author
on the PLoS One article. "This is because they have an extra copy of a key
Alzheimer's gene that leads to increased amyloid-β accumulation in the brain.
We discovered that this same protein starts to accumulate very early in the lens
of the eye, even in children, " explained Goldstein.
"The lens provides a window to the brain,"
said Moncaster, co-lead author of the study. "The lens can't clear protein
deposits the way the brain does. Our findings show that the same amyloid-β protein
that aggregates in the brain also accumulates in the lens and leads to these unusual
cataracts in Down syndrome."
"The results are striking," added David G.
Hunter, M.D., Ph.D., Ophthalmologist-in-Chief at Children's Hospital Boston and
Vice Chairman of the Department of Ophthalmology at Harvard Medical School. "We
have known that these cataracts are prevalent in people with Down syndrome and
are sometimes seen at birth, but we never knew how they were related to the disorder-now
we know," said Hunter. "These distinctive cataracts appear only in people
with advanced Alzheimer's disease and much earlier in Down syndrome."
"We are developing an eye scanner to measure amyloid-β
in the lens," said Goldstein. "This approach may provide a way for early
detection and monitoring of related pathology in the brain. Effective treatments
for the brain disease in Down syndrome and Alzheimer's disease are on the horizon,
and early detection is the key for successful intervention," he said. "The
path to effective treatment is what drives our research."
Lead co-authors on the PLoS One publication are Juliet
Moncaster (Boston University School of Medicine), Roberto Pineda (Massachusetts
Eye and Ear Infirmary, Harvard Medical School), and Robert Moir (Massachusetts
General Hospital, Harvard Medical School). Co-authors of the study are Suqian
Lu, Mark Burton, Joy Ghosh and Anca Mocofanescu and Rebecca Folkerth (Brigham
& Women's Hospital, Harvard Medical School), Maria Ericsson (Harvard Medical
School), Stephanie Soscia and Rudolph Tanzi (Massachusetts General Hospital, Harvard
Medical School), Richard Robb and David Hunter (Children's Hospital Boston, Harvard
Medical School), Jerome Kuszak (Rush University Medical Center), and John Clark
(University of Washington, Seattle). The corresponding author of the study is
Lee Goldstein (Boston University School of Medicine and Boston University Alzheimer's
Disease Center).
The five-year research effort was supported by the National
Institutes of Health (National Institute of General Medical Sciences, National
Institute on Aging), American Federation for Aging Research, Alzheimer's Association,
American Health Assistance Foundation, Cure Alzheimer's Fund, National Disease
Registry Interchange, Sun Health Research Institute, Florida Lion's Eye Bank,
and an anonymous foundation. The investigators disclosed that at the time of the
study Drs. Tanzi and Goldstein were scientific consultants to Neuroptix Corporation
and with Dr. Moir to Covance, Inc. The authors reported no commercial research
funding or other competing interests.
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