Reduced blood flow to the brain associated with early Alzheimer’s
may be caused by the contraction of cells wrapped around blood
vessels, according to a UCL-led study that opens up a new way to
potentially treat the disease.
Blood provides the brain’s energy supply in the form
of glucose and oxygen. Earlier studies have suggested the first
change in Alzheimer’s disease is a decrease in cerebral blood
flow.
The study, published today in the
journal Science and funded by the European
Research Council, Wellcome and the Wolfson Foundation, looked at
the role of pericytes, cells wrapped around capillaries that have
the ability to contract and regulate blood flow.
Researchers examined capillaries in
Alzheimer’s-affected human brain tissue and in mice bred to
develop Alzheimer’s pathology, and found that they were squeezed
by pericytes. They also applied amyloid beta protein (which
accumulates in the brains of people with Alzheimer’s) to slices
of healthy brain tissue, and found that the capillaries were
squeezed as a result.
They calculated that the constriction was severe
enough to halve blood flow, which is comparable to the decrease
in blood flow found in parts of the brain affected by
Alzheimer’s.
Lead author Dr Ross Nortley (UCL Queen Square
Institute of Neurology) said: “Our study has, for the first time,
identified the underlying mechanism behind the reduction of brain
blood flow in Alzheimer’s disease.
“Since reduced blood flow is the first clinically
detectable sign of Alzheimer’s, our research generates new leads
for possible treatments in the early phase of the
disease.”
Professor David Attwell (UCL Neuroscience, Physiology
& Pharmacology), senior author of the study, said: “Damage to
synapses and neurons in Alzheimer’s is usually attributed to the
actions of amyloid and tau proteins accumulating in the
brain.
“Our research raises the question of what fraction of
the damage is a consequence of the decrease in energy supply that
amyloid produces by constricting the brain’s finer blood
vessels.
“In clinical trials, drugs that clear amyloid beta
from the brain have not succeeded in slowing mental decline at a
relatively late phase of the disease. We now have a new avenue
for therapies intervening at an earlier stage.”
The finding raises the prospect of treatments for
Alzheimer’s that are focused on keeping the pericytes
relaxed.
