Squeezing of blood vessels may contribute to cognitive decline in Alzheimer鈥檚

21 June 2019

Reduced blood flow to the brain associated with early Alzheimer鈥檚 may be caused by the contraction of cells wrapped around blood vessels, according to a 果冻影院-led study that opens up a new way to potentially treat the disease.

Blood provides the brain鈥檚 energy supply in the form of glucose and oxygen. Earlier studies have suggested the first change in Alzheimer鈥檚 disease is a decrease in cerebral blood flow.听

The study, published today in the journal听Science听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鈥檚-affected human brain tissue and in mice bred to develop Alzheimer鈥檚 pathology, and found that they were squeezed by pericytes. They also applied amyloid beta protein (which accumulates in the brains of people with Alzheimer鈥檚) 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鈥檚.

Lead author Dr Ross Nortley (果冻影院 Neuroscience, Physiology & Pharmacology and 果冻影院 Queen Square Institute of Neurology) said: 鈥淥ur study has, for the first time, identified the underlying mechanism behind the reduction of brain blood flow in Alzheimer鈥檚 disease.听

鈥淪ince reduced blood flow is the first clinically detectable sign of Alzheimer鈥檚, our research generates new leads for possible treatments in the early phase of the disease.鈥澨�听

Professor David Attwell (果冻影院 Neuroscience, Physiology & Pharmacology), senior author of the study, said: 鈥淒amage to synapses and neurons in Alzheimer鈥檚 is usually attributed to the actions of amyloid and tau proteins accumulating in the brain.听

鈥淥ur 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鈥檚 finer blood vessels.

鈥淚n 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.鈥�

The finding raises the prospect of treatments for Alzheimer鈥檚 that are focused on keeping the pericytes relaxed.

Image

3D rendering of a one-cubic millimetre portion of mouse brain cortex, with blood vessels stained. Source:听. Credit: Antonino Paolo Di Giovanna

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Mark Greaves

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Email:听m.greaves [at] ucl.ac.uk

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