Posts tagged cholesterol
Articles and news from the latest research reports.
High good and low bad cholesterol levels are healthy for the brain, too
High levels of “good” cholesterol and low levels of “bad” cholesterol are correlated with lower levels of the amyloid plaque deposition in the brain that is a hallmark of Alzheimer’s disease, in a pattern that mirrors the relationship between good and bad cholesterol in cardiovascular disease, UC Davis researchers have found.
“Our study shows that both higher levels of HDL — good — and lower levels of LDL — bad — cholesterol in the bloodstream are associated with lower levels of amyloid plaque deposits in the brain,” said Bruce Reed, lead study author and associate director of the UC Davis Alzheimer’s Disease Center.
“Unhealthy patterns of cholesterol could be directly causing the higher levels of amyloid known to contribute to Alzheimer’s, in the same way that such patterns promote heart disease,” he said.
The relationship between elevated cholesterol and increased risk of Alzheimer’s disease has been known for some time, but the current study is the first to specifically link cholesterol to amyloid deposits in living human study participants, Reed said.
The study, “Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis,” is published online today in JAMA Neurology.
In the United States, cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood. For HDL cholesterol, a level of 60 mg/dl or higher is best. For LDL cholesterol, a level of 70 mg/dL or lower is recommended for people at very high risk of heart disease.
Charles DeCarli, director of the Alzheimer’s Disease Center and an author of the study, said it is a wake-up call that, just as people can influence their late-life brain health by limiting vascular brain injury through controlling their blood pressure, the same is true of getting a handle on their serum cholesterol levels.
“If you have an LDL above 100 or an HDL that is less than 40, even if you’re taking a statin drug, you want to make sure that you are getting those numbers into alignment,” DeCarli said. “You have to get the HDL up and the LDL down.”
The study was conducted in 74 diverse male and female individuals 70 years and older who were recruited from California stroke clinics, support groups, senior facilities and the Alzheimer’s Disease Center. They included three individuals with mild dementia, 33 who were cognitively normal and 38 who had mild cognitive impairment.
The participants’ amyloid levels were obtained using a tracer that binds with amyloid plaques and imaging their brains using PET scans. Higher fasting levels of LDL and lower levels of HDL both were associated with greater brain amyloid — a first-time finding linking cholesterol fractions in the blood and amyloid deposition in the brain. The researchers did not study the mechanism for how cholesterol promotes amyloid deposits.
Recent guidelines instituted by the American College of Cardiology, the American Heart Association and the National Heart, Lung, and Blood Institute have suggested abandoning guidelines for LDL targets. Reed said that recommendation may be an instance in which the adage that “what’s good for the heart is good for the brain” does not apply.
“This study provides a reason to certainly continue cholesterol treatment in people who are developing memory loss, regardless of concerns regarding their cardiovascular health,” said Reed, a professor in the UC Davis Department of Neurology.
“It also suggests a method of lowering amyloid levels in people who are middle aged, when such build-up is just starting,” he said. “If modifying cholesterol levels in the brain early in life turns out to reduce amyloid deposits late in life, we could potentially make a significant difference in reducing the prevalence of Alzheimer’s, a goal of an enormous amount of research and drug development effort.”
Research unveils insight into a debilitating brain disease
From the neurons that enable thought to the keratinocytes that make toenails grow-a complex canopy of sugar molecules, commonly known as glycans, envelop every living cell in the human body.
These complex carbohydrate chains perform a host of vital functions, providing the necessary machinery for cells to communicate, replicate and survive. It stands to reason, then, that when something goes wrong with a person’s glycans, something goes wrong with them.
Now, researchers at the University of Georgia are learning how changes in normal glycan behavior are related to a rare but fatal lysosomal disease known as Niemann-Pick type C (NPC), a genetic disorder that prevents the body from metabolizing cholesterol properly. The findings were published recently in the PNAS Early Edition.
"We are learning that the problems associated with cholesterol trafficking in the cell lead to problems with glycans on the cell’s surface, and that causes a multitude of negative effects," said Geert-Jan Boons, professor of chemistry in the Franklin College of Arts and Sciences and researcher at UGA’s Complex Carbohydrate Research Center. "Now, for the first time, we can see what these problems are, which we hope will lead to a new understanding of diseases like NPC."
Because NPC patients are unable to metabolize cholesterol, the waxy substance begins to accumulate in the brain. This can lead to a host of serious problems, including neurodegeneration, which the researchers hypothesize may be caused by improper recycling of glycans on the surface of an NPC patient’s cells.
Glycans normally undergo a kind of recycling process when they enter the cell only to be returned to the surface recharged and ready to work. The researchers discovered that glycans in NPC cells do not do this.
"One of the secondary effects of NPC is the disruption of traffic pathways within the cell, and this can lead to altered recycling of glycans," said Richard Steet, associate professor of biochemistry and molecular biology and CCRC researcher. "The glycans come into the cell, but they won’t recycle back up to the cell’s surface where they must exist to function as receptors or ion channels."
"Basically, the machinery gets clogged up," Boons said.
Like downed phone lines and flooded roads in a thunderstorm, glycans get stuck inside the cell making communication and travel for these cells difficult or impossible. Without these basic abilities, the body’s motor, sensory and cognitive functions begin to suffer. This might explain why NPC patients suffer from such a wide variety of neurological and psychiatric disorders, such as uncoordinated limb movements, slurred speech, epilepsy, paralysis, psychosis, dementia and hallucinations.
The researchers made these observations in fibroblasts taken from diseased patients. These cells are most commonly found in connective tissues, and they play a vital role in wound healing. However, they hope to continue their investigation into the effects of NPC by studying glycan behavior in neural cells, which make up the human brain.
While they caution that much more work must be done, they hope that an improved understanding of the roles that glycans play in neural cells will lead to new therapeutics for NPC and other diseases like it.
"It is exciting to work on projects like these, because we believe glycobiology is the next frontier, the next level of complexity," Boons said. "The time is right for new discovery."
(Source: news.uga.edu)