Alzheimer's, Dementia & Mental Health
Plaque of Alzheimer's Disease First Appears in
Retinas; Optical Imaging May Lead to Diagnosis
Noninvasive optical imaging detects retinal plaques
in live laboratory mice, suggesting the possibility of early noninvasive
diagnosis
June
24, 2010 The nerve cell-damaging plaque that builds up in the brain
with Alzheimer's disease also builds up in the retinas of the eyes and
it shows up there earlier, leading to the prospect that noninvasive
optical imaging of the eyes could lead to earlier diagnosis,
intervention and monitoring of the disease, according to new research.
Scientists discovered characteristic amyloid
plaques in retinas from deceased Alzheimer's disease patients and used a
noninvasive optical imaging technique to detect retinal plaques in live
laboratory mice genetically modified to model the human disease. The
combined results suggest the possibility that noninvasive retinal
imaging may be helpful in early diagnosis of the disease.
The research was conducted by a team of scientists
at Cedars-Sinai Medical Center in collaboration with colleagues from the
Weizmann Institute of Science in Israel and the University of Southern
California. Results were published online June 13 in the journal
NeuroImage, and related findings will be presented July 13 at the
Alzheimer's Association International Conference on Alzheimer's Disease.
Alzheimer's disease is a devastating condition that
is becoming more prevalent worldwide as the baby-boom generation
advances into its senior years, but there is no conclusive, noninvasive
way to diagnose it.
Previous studies have suggested that changes in the
brain may begin years or even decades before symptoms occur
emphasizing the need for earlier, reliable detection for early
therapeutic intervention to achieve effective remedy. The new study
suggests the possibility of monitoring Alzheimer's disease through a
simple retinal imaging approach.
Abnormal deposits in the brain called beta-amyloid
plaques, which damage cells and interrupt cell-to-cell communications,
are recognized as a hallmark sign of the disease. However, because
existing noninvasive brain-imaging technologies cannot provide
sufficient detail about these changes, the most definitive diagnosis of
Alzheimer's disease comes after an autopsy.
The research team considered the retina a better
target for noninvasive imaging of Alzheimer's disease because it is
readily accessible and, unlike other components of the eye, it is part
of the central nervous system, having a direct connection and thus many
similarities with the brain. Previous studies have documented
non-specific visual disturbances, eye disorders and certain types of
retinal abnormalities occurring with Alzheimer's disease and other
neurodegenerative conditions, but this is the first to identify human
retinal plaque deposits that could provide a specific diagnostic marker
of Alzheimer's disease.
Among the new findings:
1. In lab
tests, plaques in the retinas of mice genetically modified to model
Alzheimer's disease could be detected at a very early, pre-symptomatic
stage before the plaque appeared in the brain.
2. A
high-resolution, noninvasive optical imaging approach was developed to
monitor individual beta-amyloid plaques in the retinas of live mice. The
system is based on a harmless specific marker and the adaptation of an
existing optical system used to examine rodent eyes.
3. The
research team used a fluorescent compound called curcumin to label and
detect retinal plaques. This is believed to be the first use of curcumin
as an imaging agent to detect Alzheimer's disease-related plaques in the
retinas of live animals. Curcumin, a natural component of the spice
turmeric, binds to beta-amyloid plaques and makes them visible when
viewed microscopically. In the Cedars-Sinai research, curcumin injected
into the bloodstream of live mice crossed the blood-retinal barrier and
specifically bound to the retinal plaques, allowing them to be viewed in
high resolution with a noninvasive procedure.
4.
Observations from multiple genetically engineered mouse models of
Alzheimer's disease demonstrated a correlation between retinal plaques
and brain plaques as disease progressed.
5. In the
laboratory mice, a unique immune system-based therapy that reduces the
amount of plaques in the brain also reduced plaque load in the retina to
the same extent, suggesting that the retina could faithfully represent
the brain in assessing response to therapy.
6.
Beta-amyloid plaques were identified in retinal samples from human
patients who had died from Alzheimer's disease, and their features
correlated with the diagnosed stage of the disease. Importantly, plaques
were clearly detected not only in patients who definitely had the
disease, but also in the retinas of some people who were suspected of
having early-stage Alzheimer's disease based on clinical diagnosis and
microscopic examination of brain tissue after death.
Together, the results offer the first evidence for
the existence of Alzheimer's-specific plaques in the retina of human
patients and the ability to detect individual plaques in live mouse
models, creating a strong basis for future research building on these
findings. According to the authors, these studies establish the
potential of direct retinal beta-amyloid plaque imaging in live subjects
as a tool for early Alzheimer's disease diagnosis and prognosis, as well
as assessment of therapies.
Specialists in neurosurgery, ophthalmology, imaging
systems, neuroimmunology, pathology, neurology and biomedical
engineering collaborated on these studies, which were conducted at
Cedars-Sinai Medical Center by scientists from Cedars-Sinai, the
Weizmann Institute of Science in Israel, and the University of Southern
California.
The journal article's first authors are Maya
Koronyo-Hamaoui, Ph.D., a research scientist and assistant professor of
neurosurgery at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute and
a principal investigator in the Neuroimmunology Laboratory at
Cedars-Sinai; and Yosef Koronyo, M.Sc., LL.B., a research associate in
the departments of Surgery and Neurosurgery at Cedars-Sinai. Michal
Schwartz, Ph.D., visiting professor in the Department of Neurosurgery at
Cedars-Sinai, and the Ilze and Maurice Professorial Chair of
Neuroimmunology at the Weizmann Institute of Science in Rehovot, Israel,
is a senior author.
The work was supported by the Marciano Family
Foundation, the Maxine Dunitz Neurosurgical Institute, the U.S. Navy
Bureau of Medicine and Surgery, the National Eye Institute, the Winnick
Family Foundation, and a National Institute on Aging grant to the
University of Southern California Alzheimer's Disease Research Center.
