{"id":4627,"date":"2022-04-13T07:00:21","date_gmt":"2022-04-13T14:00:21","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/small-good-cholesterol-particles-may-have-a-role-in-alzheimers-prevention\/"},"modified":"2024-11-07T16:12:25","modified_gmt":"2024-11-08T00:12:25","slug":"small-good-cholesterol-particles-may-have-a-role-in-alzheimers-prevention","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/small-good-cholesterol-particles-may-have-a-role-in-alzheimers-prevention\/","title":{"rendered":"Small \u2018good cholesterol\u2019 particles may have a role in Alzheimer\u2019s prevention"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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\n\n \n Press Release<\/span>\n\n\n\n<\/div>\n \n \n
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Small \u2018good cholesterol\u2019 particles may have a role in Alzheimer\u2019s prevention<\/h1>\n\n\n<\/div>\n \n \n
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First-ever study to measure high-density lipoprotein particle numbers in spinal fluid led by Keck School of Medicine of USC<\/p>\n\n\n\n<\/div>\n \n

\n Wayne Lewis<\/span>\n \n April 13, 2022<\/span>\n <\/div>\n \n \n
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Keck School of Medicine of USC researchers found that a higher number of small HDL particles in spinal fluid samples was associated with two key indicators that the particles might have a protective effect against Alzheimer\u2019s disease. (Illustration iStock)<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\r\n\r\n\n\n \n \n\n\n\n\n\n\n\n
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Medical guidelines meant to reduce risk for heart disease focus on levels of cholesterol in the blood, including low-density lipoproteins (LDL), labeled \u201cbad cholesterol,\u201d and high-density lipoproteins (HDL), labeled as \u201cgood.\u201d Now, a new study suggests an important connection between good cholesterol particles in cerebrospinal fluid and brain health as well.<\/p>\n

Researchers at the Keck School of Medicine of USC took samples of cerebrospinal fluid from people aged 60 and older and measured the amount of small HDL particles in each sample. The team found that a higher number of these particles in the fluid is associated with two key indicators that the particles might have a protective effect against Alzheimer\u2019s disease.<\/p>\n

One indicator is better performance on cognitive tests. The other indicator is higher circulating levels in the cerebrospinal fluid of a particular peptide \u2014 like a protein, but smaller \u2014 called amyloid beta 42. Although that peptide contributes to Alzheimer\u2019s disease when it misfolds and clumps onto neurons, an increased concentration circulating around the brain and spine is actually linked to lower risk for the disease.<\/p>\n

\u201cThis study represents the first time that small HDL particles in the brain have been counted,\u201d said Hussein Yassine, M.D., an associate professor of medicine and neurology at the Keck School of Medicine of USC. \u201cThey may be involved with the clearance and excretion of the peptides that form the amyloid plaques we see in Alzheimer\u2019s disease, so we speculate that there could be a role for these small HDL particles in prevention.\u201d<\/p>\n

Connections between HDL and brain health<\/strong><\/p>\n

The study has just been published in the journal Alzheimer\u2019s & Dementia: The Journal of the Alzheimer\u2019s Association<\/em><\/a>. The researchers recruited 180 healthy participants with an average age of nearly 77 and analyzed samples of their blood plasma and cerebrospinal fluid. Using a sensitive technique known as ion mobility, originally developed by study co-author Ronald Krauss, M.D., at the University of California, San Francisco, the investigators were able to identify, count and measure the size of individual HDL particles. A subset of 141 participants also completed a battery of cognitive tests.<\/p>\n

Of the participants who took the cognitive tests, the ones with higher levels of small HDL particles in their cerebrospinal fluid performed better, independent of their age, sex, education or whether or not they carried the APOE4 gene, which puts them at higher risk for Alzheimer\u2019s disease. The correlation was even stronger among those who had no cognitive impairment. The evidence suggests that these HDL particles may be key to finding treatments that would work early in the disease process, long before cognitive decline occurs.<\/p>\n

\u201cWhat we\u2019re finding here is that before the onset of cognitive impairment, these oils \u2014 these small HDL particles \u2014 are lubricating the system and keeping it healthy,\u201d he said. \u201cYou\u2019ve got a 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.\u201d<\/p>\n

\u00a0<\/strong>A fresh Alzheimer\u2019s research direction and the potential for prevention<\/strong><\/p>\n

Yassine and his team were led to study HDL particles in the brain<\/a> by numerous links between good cholesterol and brain health. But first, it\u2019s helpful to know a little more about what makes good cholesterol good.<\/p>\n

Cholesterol itself is a fat necessary for the body to function, but at consistently high levels, excess cholesterol can build up in the walls of veins and arteries and poses the risk of eventual blockage that can cause a heart attack or stroke.<\/p>\n

However, the same way oil and water don\u2019t mix, cholesterol can\u2019t travel solo to get where it needs to go via the waterways of our blood. Instead, it\u2019s gathered, transported and released by balls of protein and fat called lipoproteins, including LDL and HDL. \u201cBad\u201d LDL deposits cholesterol in the body, while \u201cgood\u201d HDL collects cholesterol for breakdown, recycling and ejection by the liver.<\/p>\n

In the brain, HDL helps form the sheaths that insulate the brain and nerve cells so they can quickly communicate amongst themselves, and it plays a role in the growth and repair of neurons. It also appears to help prevent inflammation to the barrier between the brain and blood system, which can result in cognitive decline. And it may be possible that, the same way HDL gets rid of excess cholesterol and fats in the body that lead to cardiovascular disease, it helps clear off clumps of misfolded peptides and proteins before they cause damage in the brain leading to Alzheimer\u2019s disease.<\/p>\n

But unlike most HDL in the blood, HDL particles in the brain are smaller and need a protein called apolipoprotein E, or ApoE, to do their work. \u00a0The strongest risk factor for Alzheimer\u2019s disease, the APOE4 gene, is a mutation or variant of the APOE gene that encodes that very same protein.<\/p>\n

Yassine and his colleagues already have studies underway using electron microscopy \u2014 which can capture images down to the molecular level \u2014 in order to better understand the structure and function of ApoE HDL. They also hope to study ApoE HDL and Alzheimer\u2019s risk over time in larger groups of participants, with an eye toward elucidating factors such as the effects of medications and of diseases including diabetes.<\/p>\n

\u201cPeople are realizing that there is more to late-onset Alzheimer\u2019s disease,\u201d Yassine said. \u201cPerhaps it\u2019s 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.\u201d<\/p>\n

About this study<\/strong><\/p>\n

Co-first authors of the study are Ashley Martinez of the Keck School of Medicine of USC, Gali Weissberger of Bar Ilan University and Zsuzsanna Kuklenyik of the Centers for Disease Control and Prevention. Other authors are Xulei He, Cristiana Meuret, Trusha Parekh, Jon Rees, Bryan Parks, Michael Gardner, Melanie Sweeney, Michael Harrington, Xinhui Wang, Berislav Zlokovic, Elizabeth Joe, Lon Schneider, Helena Chui, John Barr and Duke Han, all of USC; Sarah King of UCSF; Timothy Collier of Quest Diagnostics in Cleveland; and Daniel Nation of the University of California, Irvine.<\/p>\n

The study was supported by the National Institutes of Health, the L.K. Whittier Foundation, the Huntington Medical Research Institutes, the Dairy Research Institute, Quest Diagnostics, Saliogen, the Della Martin Foundation, the Cure Alzheimer\u2019s Fund, the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, the Centers for Disease Control and Prevention and Washington University. The Batey Foundation funded instrumentation used for ion mobility analysis.<\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":163,"featured_media":4628,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[489,234,169,20,633,632],"class_list":["post-4627","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-alzheimers-disease","tag-department-of-neurology","tag-latest","tag-research","tag-usc-center-for-personalized-brain-health","tag-usc-zilkha-neurogenetic-institute"],"acf":[],"yoast_head":"\nSmall \u2018good cholesterol\u2019 particles may have a role in Alzheimer\u2019s prevention<\/title>\n<meta name=\"robots\" content=\"index, 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