Good Cholesterol (HDL) Particles In Cerebrospinal Fluid Play A Vital Role In Protecting The Brain


Researchers at the Keck School of Medicine of USC (University of Southern California), US have proposed a connection between good cholesterol particles in cerebrospinal fluid and brain health. Cerebrospinal fluid is a clear fluid that surrounds the brain and the spinal cord and cushions them from injury, while also providing nutrients.

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Medical guidelines made to reduce the risks of health diseases focus on levels of cholesterol in the blood, including HDL (high-density lipoproteins) known as "good cholesterol" and LDL (low-density lipoproteins) known as "bad cholesterol".

During the study, researchers took samples of cerebrospinal fluid from people aged between 60 and above and estimated the number of good cholesterol particles in each sample. The team discovered that these particles were associated with two crucial indicators that might play a defensive role against Alzheimer's disease, a neurological disorder that destroys thinking and memory skills and other important brain functions.

The researchers analyzed the samples of cerebrospinal fluid and blood plasma taken from 180 healthy participants aged nearly 77. They identified, counted and measured the size of individual HDL particles using a sensitive technique called ion mobility. This technique was originally developed by Ronald Krauss, M.D. at the University of California, San Francisco. Also, a group of 141 participants completed a series of cognitive tests.

One of the two indicators was the improved performance in the cognitive tests. The other was the higher transmitting levels in the cerebrospinal fluid of a particular peptide. This peptide is known as amyloid-beta 42, which is like a protein but smaller. This peptide causes Alzheimer's disease when it misfolds and clusters onto neurons. But the increased concentration of this peptide circulating the spine and brain can lower the risks of the disease.

“This study represents the first time that small HDL particles in the brain have been counted,” said Hussein Yassine, M.D., an Associate Professor of Medicine and Neurology at the Keck School of Medicine of USC. “They may be involved with the clearance and excretion of the peptides that form the amyloid plaques we see in Alzheimer’s disease, so we speculate that there could be a role for these small HDL particles in prevention.”


Connections Between Mental Health And HDL

Out of the participants who performed cognitive tests, the ones with the higher levels of small good cholesterol particles in their cerebrospinal fluid performed better, irrespective of their age, sex, education or whether they carried the APOE4 gene (a gene that increases the risks for Alzheimer's disease) or not. The connection was stronger among the participants with no cognitive impairment. This evidence indicated that the HDL particles might help discover the best treatments for Alzheimer's disease.

“What we’re finding here is that before the onset of cognitive impairment, these oils — these small HDL particles — are lubricating the system and keeping it healthy,” said Krauss. “You’ve got time to intervene with exercise, drugs or whatever else to keep brain cells healthy. We still need to understand the mechanisms that promote the production of these particles, in order to make drugs that increase small HDL in the brain.”


The Alzheimer's research and the Prospective for Prevention

Yassine and his team proposed the study on the HDL particles in the brain because they keep the brain healthy. These particles form the sheaths that protect the brain and nerve cells so that they can function properly. These sheaths help in the growth and repair of neurons. They also prevent inflammation to the barrier between the blood system and the brain, which can result in a cognitive reduction.

The HDL particles in the brain are smaller and require a protein called apolipoprotein E, or ApoE, to do all that work. The strongest risk factor for Alzheimer's disease is the APOE4 which is a variant of the APOE gene that encodes that very same protein.

The research team used electron microscopy, which captures images at the molecular level to understand the function and structure of the ApoE HDL. They are hoping to study Apoe HDL and Alzheimer's risk in a larger group of participants, explaining factors such as the effects of diseases including diabetes and of medications.

“People are realizing that there is more to late-onset Alzheimer’s disease,” said Yassine. “Perhaps it’s equally interesting to see how lipids are interacting with amyloid or how newer treatments can be focused not just on amyloid or tau, but also on fats and ApoE.”


A detailed study has been published in the journal Alzheimer’s Disease & Dementia.


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