Cholesterol Levels Linked to Brain Changes of Alzheimer’s Disease

Sept. 12, 2011 -- High cholesterol levels are associated with changes in the brain that are characteristic of Alzheimer’s disease, a new study shows.

For the study, which is published in the journal Neurology, researchers used blood tests to measure cholesterol in 147 Japanese adults 10 to 15 years before their deaths. Fifty of them (or 34%) had been diagnosed with dementia.

Tissue samples from their brains were then examined on autopsy.

Those who had total cholesterol levels over 224 mg/dL in mid- to late life, before they had any symptoms of Alzheimer’s, were at least seven times more likely to have beta-amyloid plaques in their brains by the time they died, compared to people whose cholesterol was under 173 mg/dL. The American Heart Association considers total cholesterol levels below 200 mg/dL to be desirable.

LDL, or “bad,” cholesterol over 155 mg/dL was also strongly associated with the likelihood of developing beta-amyloid plaques, compared to people whose LDL was lower than 106 mg/dL. People with high LDL levels were at least eight times more likely to display pathologic features of Alzheimer’s disease. Ideal LDL levels are felt to fall below 100 mg/dL, according to the AHA.

The relationship to cholesterol values remained after researchers adjusted for other things that are thought to influence the risk of Alzheimer’s disease, like age, sex, body weight, aerobic exercise, blood pressure, a history of stroke, and blood sugar and insulin levels.

Cholesterol and the Brain

Beta-amyloid is a sticky protein that clogs the brains of people who have Alzheimer’s disease.

Though researchers aren’t sure how beta-amyloid is related to the memory loss and other changes that occur with Alzheimer’s, one theory is that plaques that form between nerve cells may jam the brain’s communication network.

“Our study suggests that serum cholesterol in excess of a certain threshold level would trigger the plaque formation,” says study researcher Kensuke Sasaki, MD, an assistant professor of neuropathology at Kyushu University in Fukuoka, Japan, says in an email to WebMD.

People who keep their cholesterol down as they age might therefore be able to reduce the risk of plaque formation, Sasaki says.

In Alzheimer’s, plaques are usually found in conjunction with another problem called tangles. Tangles are twisted fibers of tau protein that build up inside nerve cells.

It had been thought that a buildup of beta-amyloid might cause tangles and that growing numbers of tangles in the brain might lead to Alzheimer’s symptoms.

Curiously, though, the study found that while cholesterol seemed to be associated with the development of plaques, it did not seem to influence tangles.

“This study lends credence to the notion that there may be different factors driving amyloid pathology versus tangle pathology,” says Marc L. Gordon, MD, chief of Neurology at Zucker Hillside Hospital in Glen Oaks, N.Y. and an Alzheimer’s researcher at The Feinstein Institute for Medical Research in Manhasset, N.Y.

He says the study may mean that sequence of brain damage in Alzheimer’s is less straightforward than “amyloid causes tangles causes disease,” Gordon says.

Important Questions Remain

Experts who reviewed the study for WebMD say its findings are valuable, since few studies have been able to connect blood cholesterol levels to physical changes that happen years later in the brain.

“There’s actually fairly little data on the relationship between cholesterol and Alzheimer’s disease pathology in humans,”says Zoe Arvanitakis, MD, an associate professor in the department of neurological sciences at Rush University Medical Center in Chicago.

“And really there’s little known about the relationship of cholesterol in earlier life to the development of Alzheimer’s disease in later life, and this study tried to get at those two points,” Arvanitakis says.

But Arvanitakis and other experts say the study has important weaknesses that limit what it can say.

“There’s a lot of missing pieces in the chain of evidence in this study,” says Adam Rosenblatt, MD, director of neuropsychiatry at the Johns Hopkins School of Medicine in Baltimore.

Rosenblatt says that although scientists have long suspected that cholesterol plays a role in Alzheimer’s disease, it is still not clear what that may be.

For example, “Studies that have tried to treat or prevent Alzheimer’s disease by lowering cholesterol” using statin medications “have not produced convincing evidence,” he says.

There’s not even enough evidence to show that plaques in the brain cause Alzheimer’s symptoms.

It could be that the disease, he says, is somehow causing both higher cholesterol levels and plaques in the brain, rather than the other way around.

“You really couldn’t conclude from this study that cholesterol causes Alzheimer’s or even makes it more likely, or that lowering your cholesterol would prevent it,” Rosenblatt says.