Cholesterol—Good for the brain, bad for the heart

January 23, 2017
C. Ronald Kahn, M.D., is Chief Academic Officer at Joslin Diabetes Center. Dr. Kahn is co-head of the section on Integrative Physiology & Metabolism and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. Credit: John Soares

Healthy brains need plenty of cholesterol for nerve cells to grow and work properly, but diabetes can reduce the amount of cholesterol in the brain, as a Joslin Diabetes Center team has demonstrated. Joslin researchers and their colleagues now have gone on to show that mice that are genetically modified to suppress cholesterol production in the brain show dramatic symptoms of neurological impairment.

This finding may help to explain why the risk of developing Alzheimer's disease increases in diabetes, says Heather Ferris, M.D., Ph.D., a Joslin research associate and lead author on a paper about the work published in PNAS.

Scientists have long studied the roles of cholesterol in Alzheimer's, one reason being that mutations in a cholesterol-carrying protein known as APOE are the strongest genetic risk factor for the disease, Ferris points out.

Astrocytes, an important class of supporting cells in the brain, are thought to produce most of its cholesterol. In their latest study, the Joslin researchers created a mouse model in which a gene known as SREBP2, the master regulator of , has been knocked out.

The results were striking. "Compared to normal animals, these mice have very small brains, and multiple behavioral abnormalities," says Ferris.

"Not only do these mice have trouble learning and remembering, they can't perform some other normal daily behaviors such as building a nest," adds C. Ronald Kahn, M.D., senior author on the paper, Joslin's chief academic officer and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. "Some of these effects were a little bit like Alzheimer's disease in the mouse, except that they were much more severe."

Curiously enough, the mice also displayed changes in their whole-body metabolism, burning more carbohydrates and gaining less weight.

"We're only at the beginning of this research on how diabetes and Alzheimer's disease could be related, but cholesterol could be a mediator," says Ferris. While investigators in other labs have suggested that raised rather than lower levels of cholesterol may be linked to brain disorders, "we think our model may be more clinically relevant," she says.

Drugs that reduce in the cardiovascular system can strongly benefit people with diabetes or related conditions, but cholesterol in the blood generally can't cross into the brain, and is quite different in the brain, she points out.

Going forward, the researchers are creating mouse models that will combine the lowered-brain-cholesterol model with models of Alzheimer's disease or type 1 diabetes or type 2 diabetes. The scientists also will look at the effects of brain deprivation in adult mice, in addition to mice born with the modification.

"This work gives another example of how research in one field of biomedicine can affect knowledge in another field," Kahn comments. "We didn't start out thinking about Alzheimer's ; we were trying to understand the effects of in the brain."

Explore further: Protein linked to high risk of Alzheimer's can be removed from brain without hindering learning

More information: Heather A. Ferris et al. Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1620506114

Related Stories

Protein linked to high risk of Alzheimer's can be removed from brain without hindering learning

October 4, 2016
A protein linked to higher risk of Alzheimer's can be removed from the brains of mice without hindering memory and learning, according to a study that addresses whether potential therapeutics targeting this protein would ...

High cholesterol intake and eggs do not increase risk of memory disorders

January 9, 2017
A new study from the University of Eastern Finland shows that a relatively high intake of dietary cholesterol, or eating one egg every day, are not associated with an elevated risk of dementia or Alzheimer's disease. Furthermore, ...

Study reveals link between high cholesterol and Alzheimer's disease

September 12, 2011
People with high cholesterol may have a higher risk of developing Alzheimer's disease, according to a study published in the September 13, 2011, issue of Neurology, the medical journal of the American Academy of Neurology.

Alzheimer's researchers investigate diabetes link in mice

June 22, 2016
Researchers in Aberdeen have highlighted a possible new link between Alzheimer's disease and diabetes according to a new study published today in the journal Diabetologia.

Researchers find direct link between insulin resistance and behavioral disorders

March 2, 2015
People with diabetes are more prone to anxiety and depression than those with other chronic diseases that require similar levels of management. The reasons for this aren't well understood, but Joslin Diabetes Center researchers ...

Recommended for you

Early study shows shoe attachment can help stroke patients improve their gait

December 14, 2017
A new device created at the University of South Florida – and including a cross-disciplinary team of experts from USF engineering, physical therapy and neurology – is showing early promise for helping correct the signature ...

Scientists rewrite our understanding of how arteries mend

December 13, 2017
Scientists from The University of Manchester have discovered how the severity of trauma to arterial blood vessels governs how the body repairs itself.

Deadly heart rhythm halted by noninvasive radiation therapy

December 13, 2017
Radiation therapy often is used to treat cancer patients. Now, doctors at Washington University School of Medicine in St. Louis have shown that radiation therapy—aimed directly at the heart—can be used to treat patients ...

Ultra-thin tissue samples could help to understand and treat heart disease

December 12, 2017
A new method for preparing ultra-thin slices of heart tissue in the lab could help scientists to study how cells behave inside a beating heart.

Young diabetics could have seven times higher risk for sudden cardiac death

December 12, 2017
Young diabetics could have seven times more risk of dying from sudden cardiac arrest than their peers who don't have diabetes, according to new research.

Research reveals how diabetes in pregnancy affects baby's heart

December 12, 2017
Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have discovered how high glucose levels—whether caused by diabetes or other factors—keep heart cells from maturing ...

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.