Scientists Closing In On How Increased Alzheimer's Risk Is Linked To Fat And Cholesterol Transport In The Brain

October 27, 1997

Scientists studying the brain are learning how the removal of cholesterol and the proper delivery of fatty compounds are vital for the healthy function of the brain, in an effort to understand how these processes gone awry can lead to Alzheimers disease.

Despite the fact that the brain is 70 percent fat, scientists have known little about how fats, or lipids, are metabolized and transported within it. The interest intensified several years ago with the surprising discovery that an increased risk of Alzheimers disease was linked to a natural genetic variant of a key fat-transporter molecule called apolipoprotein E, or apoE.

Now a team of scientists led by Mary Jo LaDu in the department of pathology at the University of Chicago Medical Center has shown that the apoE-containing fat transporters found in brain cells are very different from the apoE particles found elsewhere in the body and contain most of their cholesterol in a different form. The study may give new insights into how one variant, apoE4, found in 15 percent of the population, can increase a person's risk of developing Alzheimers.

People who inherited a copy of the apoE4 gene from one parent have been found to have a three-fold greater risk of the disease, while those who inherited a copy from both parents have eight times the risk.

The new findings were reported at the annual meeting of the Society for Neuroscience in New Orleans on October 27.

The brain is constantly moving around huge amounts of fat and cholesterol because these compounds are major components of cell membranes, which the nervous system must constantly rearrange as it makes and breaks links from cell to cell.

"If there's one organ in your body that needs to be plastic and adaptible, its your brain," LaDu says. "It's constantly making new synaptic junctions that allow you to form a thought or hold a memory."

The brain must have a dependable source of cholesterol, LaDu says, because it is a vital component of membranes; however, the brain needs to be able to clear the excess because it is also very toxic to the sensitive nerve cells.

How the brain is able to maintain such exquisite balance has been perplexing. In the blood, fats and cholesterol are packaged, with key protein components, into particles called lipoproteins. But the brain is shielded from these particles by the so-called blood-brain barrier. Instead, the brain makes its own supply of lipoprotein particles using some of the same protein components, including apoE.

LaDu's team analyzed lipoproteins found in the cerebrospinal fluid (CSF) that bathes the entire nervous system. They also compared the CSF lipoproteins with those secreted by astrocytes, helper cells in the brain that nourish and support the firing nerve cells.

The differences between the lipoproteins secreted by astrocytes and those found in the CSF suggest that the astrocytes produce particles that help the brain rid itself of excess cholesterol in addition to helping deliver membrane components to the nerve cells.

"We think this is an early but landmark study that opens up the field of brain research to the analysis of lipoproteins, which are clearly crucial to normal function," LaDu said. "ApoE also gives us another tool to try to dissect the causes of Alzheimers disease."

LaDu's team at the University of Chicago includes Catherine Reardon, Ph.D., Godfrey S. Getz, M.D./Ph.D., Vi Cabana, Ph.D., Sean Gilligan, and John Lukens, as well as Linda Van Eldik, Ph.D. at Northwestern University Medical School and David Holtzman, M.D. at Washington University School of Medicine.

. The work was funded by the National Institutes of Health, American Health Assistance Foundation, and the Alzheimer's Association.
-end-


University of Chicago Medical Center

Related Cholesterol Articles from Brightsurf:

Cholesterol's effects on cellular membranes
The findings have far-reaching implications in the general understanding of disease, the design of drug delivery methods, and many other biological applications that require specific assumptions about the role of cholesterol in cell membranes.

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

Microbes might manage your cholesterol
Researchers discover a link between human blood cholesterol levels and a gene in the microbiome that could one day help people manage their cholesterol through diet, probiotics, or entirely new types of treatment.

Experimental cholesterol-lowering drug effective at lowering bad cholesterol, study shows
Twice-yearly injections of an experimental cholesterol-lowering drug, inclisiran, were effective at reducing low-density lipoprotein (LDL) cholesterol, often called bad cholesterol, in patients already taking the maximum dose of statin drugs, according to data of the ORION-10 trial presented Saturday, Nov.

Rethinking how cholesterol is integrated into cells
Cholesterol is best known in connection with cardiovascular disease, but cholesterol is also vital for many fundamental processes in the body.

Seed oils are best for LDL cholesterol
Using a statistical technique called network meta-analysis, researchers have combined the results of dozens of studies of dietary oils to identify those with the best effect on patients' LDL cholesterol and other blood lipids.

Cholesterol leash: Key tethering protein found to transport cellular cholesterol
Cholesterol is an essential component of living organisms, but the mechanisms that transport cholesterol inside the cell are poorly understood.

New way to treat cholesterol may be on the horizon
A breakthrough discovery by scientists at Houston Methodist Research Institute could change the way we treat cholesterol.

How low should LDL cholesterol go?
New analysis shows that in a high-risk population, achieving ultra-low LDL cholesterol levels, down to <10 mg/dL, safely results in additional lowering of risk of cardiovascular events.

Does boosting 'good' cholesterol really improve your health?
A new review addresses the mysteries behind 'good' HDL cholesterol and why boosting its levels does not necessarily provide protection from cardiovascular risk for patients.

Read More: Cholesterol News and Cholesterol Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.