Blood vessels in older brains break
down, possibly leading to Alzheimer's
USC study finds breakdown in brain's
memory and learning center can be detected before cognitive loss begins,
important implications for dementia patients
21, 2014 Another puzzle to preventing risks that can lead to
Alzheimer's disease may have been solved by neuroscientists at the
University of Southern California. The brain's protective blood barrier
becomes leaky with age, starting at the hippocampus, a critical learning
and memory center that is damaged by Alzheimer's disease.
Researchers at Keck Medicine of USC
used high-resolution imaging of the living human brain to make this
first time discovery.
The study indicates it may be
possible to use brain scans to detect changes in blood vessels in the
brains hippocampus before they cause irreversible damage, which can
lead to dementia characterized by progressive loss of memory, cognition
These findings would have broad
implications on conditions that will affect 16 million American senior
citizens over age 65 by 2050, according to the latest figures from the
Alzheimer's Association. The research appears in the Jan. 21, 2015,
edition of the peer-reviewed scientific journal Neuron.
"This is a significant step in
understanding how the vascular system affects the health of our brains,"
said Berislav V. Zlokovic, M.D., Ph.D., director of the Zilkha
Neurogenetic Institute (ZNI) at the Keck School of Medicine, the Mary
Hayley and Selim Zilkha Chair for Alzheimer's Disease Research and the
study's principal investigator.
"To prevent dementias including
Alzheimer's, we may need to come up with ways to reseal the blood-brain
barrier and prevent the brain from being flooded with toxic chemicals in
the blood. Pericytes are the gate-keepers of the blood-brain barrier and
may be an important target for prevention of dementia."
Alzheimer's disease is the most
common type of dementia, a general term for loss of memory and other
mental abilities. According to the Alzheimer's Association, roughly 5.2
million people of all ages in the United States today have Alzheimer's
disease, an irreversible, progressive brain disease that causes problems
with memory, thinking and behavior.
Post-mortem studies of brains with
Alzheimer's disease show damage to the blood-brain barrier, a cellular
layer that regulates entry of blood and pathogens into the brain. The
reasons why and when this damage occurs, however, remain unclear.
In the Neuron study, Zlokovic's research team examined
contrast-enhanced brain images from 64 human subjects of various ages
and found that early vascular leakage in the normally aging human brain
occurs in the hippocampus, which normally shows the highest barrier
properties compared to other brain regions.
The blood-brain barrier also showed
more damage in the hippocampal area among people with dementia than
those without dementia, when controlling for age.
To validate the research method,
the USC team examined brain scans of young people with multiple
sclerosis without cognitive impairment, finding no difference in barrier
integrity in the hippocampus between those of the same age with and
without the disease.
The researchers also looked at the
subjects' cerebrospinal fluid (CSF), which flows through the brain and
spinal cord. Individuals who showed signs of mild dementia had 30
percent more albumin, a blood protein, in their CSF than age-matched
controls, further indicating a leaky blood-brain barrier.
The CSF of individuals with
dementia also showed a 115 percent increase of a protein related to
pericyte injury. Pericytes are cells that surround blood vessels and
help maintain the blood brain barrier; previous research has linked
pericytes to dementia and aging.
Study participants were recruited
through the USC Alzheimer's Disease Research Center and Huntington
Medical Research Institute.
Other USC co-authors include Axel
Montagne, Melanie D. Sweeney, Matthew R. Halliday, Abhay P. Sagare, Zhen
Zhao, Arthur W. Toga, Collin Y. Liu, Lilyana Amezcua, Helena C. Chui and
The study was supported by various
National Institutes of Health agencies, the Zilkha Senior Scholar
program and L. K. Whittier Foundation.
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