Is Alzheimer's caused by disruptions to the brain's energy supply?

April 4, 2018 by Kira Shaw And Orla Bonnar, The Conversation
Credit: Raytron/Shutterstock.com

It is well known that Alzheimer's disease, the most common form of dementia, involves the accumulation of sticky proteins (plaques and tangles) in the brain. But we still don't know what the root cause of the disease is. Given that someone, somewhere in the world, is diagnosed with dementia every three seconds, there is an urgent race to discover the causes of the disease so that treatments can be developed.

Scientists know that changes to the brain's happen before plaques and tangles appear and this has led to an interesting theory of the causes of the , known as the vascular hypothesis.

When become active, they need energy in the form of glucose and oxygen, which is delivered by an increase in supply to that part of the brain. But in Alzheimer's disease the blood supply is often impaired, so the amount of energy supplied to the brain cells is compromised. One of the reasons for the breakdown in this energy supply may be explained by a breakdown in the .

Capillaries in the brain are lined with very tightly packed endothelial cells that form a semi-permeable barrier. They let oxygen, glucose and other necessary substances across the barrier, but stop larger molecules from crossing into the brain. Research has shown that in people with Alzheimer's, the integrity of this barrier is compromised due to gaps forming in the usually tightly packed endothelial cells. This leads to a build-up of harmful molecules in the brain, which in turn results in swelling of the brain and reduced blood flow in it.

A lack of oxygen to the brain (a condition known as "hypoxia") has been shown to lessen the ability of neurons to fire and to alter brain chemistry. This causes brain swelling, lesions and, importantly, helps the formation of beta-amyloid plaques and tau tangles – the hallmark features of Alzheimer's. So the degeneration of these blood vessels in the brain may form a vicious cycle, eventually resulting in mass cell death.

The role of the APOE gene

Another hint that Alzheimer's disease may be caused by to the brain comes from genetics.

Plaques (in yellow) clumping on a neuron. Credit: Juan Gaertner/Shutterstock.com

The gene associated with the highest risk of developing Alzheimer's disease later in life is called APOE. Everyone inherits two copies of this gene, one from each parent, and APOE exists in three variants (alleles), called e2, e3 and e4. People with two copies of the e4 variant of the gene ("APOE4") increase their risk of developing Alzheimer's disease by about three to five times.

Researchers from John Hopkins University showed that people with the APOE4 gene had reduced brain blood flow, without any symptoms of Alzheimer's disease. And a separate study, using genetically engineered mice with the human APOE genes, showed that APOE4 resulted in damage to the capillaries before any decline in brain-cell activity became evident. These findings support the idea that blood flow disruptions may be one of the earliest changes in Alzheimer's disease.

A vascular theory of Alzheimer's disease may also explain why people who have high blood pressure, or who have had a stroke, are more likely to develop the disease. High blood pressure can cause blood clots to form in the arteries leading to your brain, which reduces blood flow and oxygenation.

A stroke may occur as a result of such , meaning the to a part of the brain is suddenly cut off. Both of these conditions decrease the energy supply to the brain, which can damage brain cells significantly.

We need a different target

There are no cures for Alzheimer's disease, only drugs to manage some of the symptoms. The new treatments that are being investigated tend to focus on removing plaques, which may or may not recover function. But perhaps a better target for drug developers would be medicines that treat changes to the blood vessels, before brain cells are affected.

In a 2012 study, published in Nature, researchers at the University of Rochester gave an immunosuppressant drug called cyclosporine to mice with the human APOE4 gene. They showed that, following this treatment, the early damage to capillaries and the blood-brain barrier were recovered. Clearly, genetically modified mice are not the same as humans, but the findings do lend further support to the vascular hypothesis.

And more than just shedding light on new drug treatment options, the vascular hypothesis also emphasises the importance of maintaining good cardiovascular health. Physical activity increases your heart rate and the blood flow to the brain, which increases oxygenation and improves the general health of your cells. As the saying goes, an ounce of prevention is worth a pound of cure.

Explore further: Antibody removes Alzheimer's plaques, in mice

Related Stories

Antibody removes Alzheimer's plaques, in mice

March 26, 2018
Years before people start showing characteristic symptoms of Alzheimer's disease, sticky plaques begin forming in their brains, damaging nearby cells. For decades, doctors have sought ways to clear out these plaques as a ...

Faults in the blood-brain barrier implicated in dementia

February 6, 2018
California based researchers have found that damage to cells known as pericytes, which surround small blood vessels in the brain, may trigger a chain of events that results in brain degeneration. The findings are published ...

Alzheimer's disease might be a 'whole body' problem

October 31, 2017
Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scientists indicates that it could be triggered by breakdowns ...

ApoE4 Alzheimer's gene causes brain's blood vessels to leak, die

May 16, 2012
Common variants of the ApoE gene are strongly associated with the risk of developing late-onset Alzheimer's disease, but the gene's role in the disease has been unclear. Now, researchers funded by the National Institutes ...

Here's what we think Alzheimer's does to the brain

November 6, 2017
Around 50m people worldwide are thought to have Alzheimer's disease. And with rapidly ageing populations in many countries, the number of sufferers is steadily rising.

Neuroscientists gain insight into cause of Alzheimer's symptoms

November 23, 2015
Virginia Tech Carilion Research Institute scientists have uncovered a mechanism in the brain that could account for some of the neural degeneration and memory loss in people with Alzheimer's disease.

Recommended for you

Rate of dementia on the decline—but beware of growing numbers

April 17, 2018
The good news? The rate of older Americans with dementia is on the decline.

Research offers potential insight into Alzheimer's disease

April 16, 2018
Slightly elevated beta-amyloid levels in the brain are associated with increased activity in certain brain regions, according to a new study from the Center for Vital Longevity (CVL) at The University of Texas at Dallas.

Americans with a college education live longer without dementia and Alzheimer's

April 16, 2018
Education gives people an edge in their later years, helping them to keep dementia at bay and their memories intact, a new USC-led study has found.

Evidence mounts for Alzheimer's, suicide risks among youth in polluted cities

April 13, 2018
A University of Montana researcher and her collaborators have published a new study that reveals increased risks for Alzheimer's and suicide among children and young adults living in polluted megacities.

Improving brain function in Alzheimer's disease mouse model

April 11, 2018
Using two complementary approaches to reduce the deposits of amyloid-beta in the brain rather than either approach alone improved spatial navigation and memory in a mouse model of Alzheimer's disease. These findings suggest ...

Sleepless nights show ties to Alzheimer's risk

April 10, 2018
Even one night of lost sleep may cause the brain to fill with protein chunks that have long been linked to the development of Alzheimer's disease, a new study warns.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.