{"id":394763,"date":"2025-11-21T13:57:15","date_gmt":"2025-11-21T13:57:15","guid":{"rendered":"https:\/\/www.europesays.com\/us\/394763\/"},"modified":"2025-11-21T13:57:15","modified_gmt":"2025-11-21T13:57:15","slug":"targeting-brain-immune-cells-could-restore-alzheimers-related-lipid-imbalance-ut-health-san-antonio-research-shows","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/394763\/","title":{"rendered":"Targeting brain immune cells could restore Alzheimer\u2019s-related lipid imbalance, UT Health San Antonio research shows"},"content":{"rendered":"

Contact: Steven Lee, 210-450-3823, lees22@uthscsa.edu<\/a>
Content by Claire Kowalick<\/p>\n

SAN ANTONIO, Nov. 20, 2025 \u2013<\/strong> More than a century ago, Alois Alzheimer noted unusual changes in brain fats, which he described as \u201clipoid granules,\u201d along with the buildup of amyloid-beta (amyloid) plaques and tau protein tangles. These observations led to the identification of Alzheimer\u2019s disease and related dementias. Since then, most Alzheimer\u2019s research has focused on amyloid and tau, while brain lipid abnormalities have received far less attention.<\/p>\n

New research from UT Health San Antonio, the academic health center of The University of Texas at San Antonio<\/a>, in collaboration with the University of California at Irvine, shows that changes in brain fats, or lipids, play a major role in Alzheimer\u2019s development and progression. Lipid imbalances can influence how amyloid proteins build up, and certain genes that regulate lipid metabolism are linked to Alzheimer\u2019s risk.<\/p>\n

\"\"Juan Pablo Palavicini, PhD<\/p>\n

\u201cThe brain is a unique organ,\u201d said Juan Pablo Palavicini, PhD<\/a>, assistant professor in the Department of Cellular and Integrative Physiology at UT San Antonio\u2019s Long School of Medicine, and co-lead of the study. \u201cUnlike most other organs, which are rich in protein, more than half of the brain\u2019s dry weight is made up of different kinds of lipids, including cholesterol, phospholipids and sphingolipids. In Alzheimer\u2019s disease, we see massive disruption of these lipids, yet most studies focus only on genes and proteins.\u201d<\/p>\n

The study, published Oct. 15 in Nature Communications<\/a>, reveals how microglia, the brain\u2019s immune cells, control some of these lipid changes. Depending on how they are manipulated, microglia can either help maintain balance or worsen the disease. The research was co-led by Palavicini and Xianlin Han, PhD<\/a>, professor in the Department of Medicine, who are both investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies<\/a>.<\/p>\n

Testing microglia\u2019s role
<\/strong><\/p>\n

Using a mouse model of Alzheimer\u2019s, the scientists tested two approaches to remove microglia. In one, they treated mice with a drug that nearly eliminated all microglia and in the other, they used genetically modified mice that lacked microglia. These strategies allowed researchers to separate effects caused by microglia from those caused by other brain cells.<\/p>\n

\u201cWe wanted to understand which cells are driving these lipid changes,\u201d Palavicini said. \u201cSome lipids go up, some go down, but which cell types are responsible? By removing microglia, we could see which changes depend on them and which do not.\u201d<\/p>\n

The research team compared results from the mouse studies with post-mortem brain samples from people with and without Alzheimer\u2019s.<\/p>\n

They found that amyloid buildup dramatically altered brain lipid patterns. Two groups of lipids stood out: lysophospholipids (LPC and LPE), which are linked to inflammation and oxidative stress, and bis(monoacylglycero)phosphate (BMP), a lipid that helps regulate the cell\u2019s \u201crecycling centers,\u201d called lysosomes. The research team found that a form of BMP containing arachidonic acid (AA-BMP) accumulated near amyloid plaques, and that long-term removal of microglia prevented AA-BMP buildup, showing that microglia drive these changes.<\/p>\n

\u201cBMP is still not well understood, especially in the brain,\u201d Palavicini said. \u201cIt forms substructures in lysosomes that attract proteins to break down damaged lipids. Without microglia, AA-BMP levels drop, which can interfere with the brain\u2019s cleanup processes.\u201d<\/p>\n

Progranulin\u2019s key effects
<\/strong><\/p>\n

The protein progranulin, made by both microglia and neurons, emerged in the study as a key lipid regulator. Progranulin levels rise in Alzheimer\u2019s conditions and closely align with AA-BMP accumulation. Removing microglia lowered both progranulin and AA-BMP near plaques, suggesting that microglial progranulin helps regulate lipid balance.<\/p>\n

\u201cIn the Alzheimer\u2019s brain, rather than lowering BMP, it may be important to maintain or support its levels,\u201d Palavicini said. \u201cProgranulin helps maintain this lipid and protect neurons. Therapies that boost progranulin could potentially restore balance and support brain health.\u201d<\/p>\n

Influence from other brain cells
<\/strong><\/p>\n

Not all lipids are controlled by microglia. LPC and LPE levels were mostly influenced by astrocytes and neurons. LPC buildup was tied to astrocyte activation and enzyme activity, while LPE increases were linked to oxidative stress and weakened antioxidant defenses.<\/p>\n

\u201cEven though we hypothesized microglia were driving the accumulation of these inflammatory lipids, it was actually other cell types, including astrocytes,\u201d Palavicini said. \u201cThis distinction helps us understand which cells to target for therapies and shows how complex lipid regulation is in Alzheimer\u2019s disease.\u201d<\/p>\n

Microglia protect myelin and neurons
<\/strong><\/p>\n

The study revealed that microglia also help maintain myelin, a protective coating around neurons. Genetic removal of microglia under amyloid stress reduced myelin-related lipids.<\/p>\n

\u201cThe microglia are helping neurons, and if you remove them, neurons seem to experience more oxidative stress,\u201d Palavicini said. \u201cThis is why some lipid levels increase when microglia are gone. In most cases, removal of microglia was damaging, which was somewhat unexpected but reveals how critical they are for brain lipid metabolism.\u201d<\/p>\n

More complete picture of Alzheimer\u2019s
<\/strong><\/p>\n

This research shows that Alzheimer\u2019s is not just about amyloid plaques and tau tangles. It also involves disrupted lipid balance, with microglia, astrocytes and neurons each playing different roles. Microglia maintain protective lipids like BMP and support myelin, while astrocytes and neurons drive other changes, including lysophospholipid accumulation and oxidative stress.<\/p>\n

\u201cUnderstanding which cells regulate which lipids opens the door to more precise therapies,\u201d Palavicini said. \u201cBy targeting lipid balance along with amyloid and tau, we can develop better strategies to protect neurons and potentially slow or prevent Alzheimer\u2019s disease.\u201d<\/p>\n


Microglia-specific regulation of lipid metabolism in Alzheimer\u2019s disease revealed by microglial depletion in 5xFAD Mice<\/strong><\/p>\n

Ziying Xu, Sepideh Kiani Shabestari, Savannah Barannikov, Kevin F. Bieniek, Mathew Blurton-Jones, Juan Pablo Palavicini, Xianlin Han<\/p>\n

Published: Oct. 15, 2025, Nature Communications<\/p>\n

Link to full study: https:\/\/www.nature.com\/articles\/s41467-025-64161-z<\/a><\/p>\n

\u00a0<\/p>\n

UT Health San Antonio<\/a> is the academic health center of The University of Texas at San Antonio (UT San Antonio), offering a comprehensive network of inpatient and outpatient care facilities staffed by medical, dental, nursing and allied health professionals who provide more than 2.5 million patient visits each year. It is the region\u2019s only academic health center and\u00a0one of the nation\u2019s leading health sciences institutions, supported by the schools of medicine, nursing, dentistry, health professions, graduate biomedical sciences and public health that\u00a0are leading change and advancing health-related fields throughout South Texas and the world. To learn about the many ways \u201cWe make lives better\u00ae,\u201d visit UTHealthSA.org<\/a>.<\/p>\n

The Joe R. and Teresa Lozano Long School of Medicine<\/a> at The University of Texas at San Antonio (UT San Antonio) is listed among\u00a0U.S. News & World Report\u2019s\u00a0best medical schools, among the top 5% of universities globally for clinical medicine research and ranked as the third-highest medical school in Texas for medical research funding by the National Institutes of Health. The Long School of Medicine supports the university\u2019s academic health center, UT Health San Antonio.<\/p>\n

The Sam and Ann Barshop Institute for Longevity and Aging Studies <\/a>at UT Health San Antonio is one of the world\u2019s premier institutes dedicated to the study of age-related diseases. The Barshop Institute is the only aging-intensive research institute in the country to have four peer-reviewed designations: two National Institute on Aging (NIA)-funded centers (Nathan Shock and Claude D. Pepper centers), a testing site of the NIA-sponsored Interventions Testing Program, and a U.S. Department of Veterans Affairs Geriatric Research, Education and Clinical Center. UT Health San Antonio is the academic health center of The University of Texas at San Antonio (UT San Antonio).<\/p>\n

Stay connected with UT Health San Antonio on\u00a0Facebook<\/a>, Twitter<\/a>, LinkedIn<\/a>,\u00a0Instagram<\/a> and\u00a0YouTube<\/a>.<\/p>\n

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