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UCLA

desert

Climate Change, Not Rain Shortage, Drives Severe Western Droughts

Categories Earth, Energy & Environment

illustration of gut bacteria

Discrimination’s Hidden Impact: Study Reveals Distinct Changes in Gut Bacteria

Categories Brain & Behavior, Health, Social Sciences

ENPP1 is expressed in the region of scarring after injury to the heart. Cardiac muscle shown in red and ENPP1 in green demonstrates expression of ENPP1 in the region of scar formation.

Researchers engineer experimental drug for preventing heart failure after heart attacks

Categories Health

Fluorescent image of a developing human hippocampus.

Study Maps DNA Modifications in Developing Human Brain

Categories Brain & Behavior

Happy woman. Pixabay

Study finds common breast cancer treatments may speed aging process

Categories Health

Patient and doctor

UCLA Study Reveals Key Factors in Testosterone Recovery After Prostate Cancer Treatment

Categories Health

sad looking boy on a couch

Childhood Trauma’s Long-Term Health Impacts Differ by Sex, UCLA Study Finds

Categories Brain & Behavior

Neurons. Alzheimer’s disease varies widely in its age of onset, presentation, and severity. Recently, the SORL1 gene has received increased attention since variations in this gene have been associated with both early- and late-onset Alzheimer’s. However, little is known about how damage to SORL1 leads to disease. Using stem cells from patients with Alzheimer’s, investigators from Harvard-affiliated Brigham and Women’s Hospital found that loss of normal SORL1 function leads to a reduction in two key proteins known to be involved in Alzheimer’s and which play an essential role in the neurons of healthy individuals. Their results, published in Cell Reports, suggest a potential strategy for Alzheimer’s disease treatment, especially for patients not responsive to existing therapies. In this new study, the researchers utilized a stem-cell based approach that examined natural genetic variability in Alzheimer’s patients to gain insight into an alternative pathway driving disease. The researchers used CRISPR technologies to remove the SORL1 gene from progenitor stem cells, derived from participants in two Alzheimer’s research cohorts, the Religious Order Studies and Rush Memory and Aging Project. They then programmed the stem cells to differentiate into four different kinds of brain cells to examine the impact of removing SORL1 on each cell type. The most dramatic impact was seen in neurons and a “support” cell in the brain (astrocytes). Neurons lacking SORL1 demonstrated especially prominent reduction in the levels of two key Alzheimer’s disease proteins: APOE and CLU. Without APOE and CLU, neurons cannot properly regulate lipids, which accumulate in droplets that may impair neurons’ abilities to communicate with each other. The researchers verified their lab-based results by examining natural genetic variation in SORL1 expression in the brain tissue of 50 members of the cohorts, finding again that lower SORL1 activity in neurons was correlated with reduced APOE and CLU in these people. Historically, researchers have studied three potent genetic drivers of Alzheimer’s disease (APP, PSEN1 and PSEN2), which are commonly mutated in hereditary, early-onset Alzheimer’s (AD diagnosis before age 65). Preclinical models and cell-based systems largely rely on mutations in these genes to model Alzheimer’s disease, even though in many people with late-onset (“sporadic”) Alzheimer’s, a more complex interaction between genes, lifestyle, and environment determines the presentation of the disease. Key neurological features of Alzheimer’s disease, including the abundance of amyloid-beta plaques in the brain, also vary across individuals. “Our study is one of the first with human cells from a large collection of individuals to try to understand the ‘molecular road’ that starts with SORL1, which we now see converges with APOE,” said corresponding author Tracy Young-Pearse of the Ann Romney Center for Neurological Diseases. “Our research points to the importance of developing interventions that target these and other molecular roads to Alzheimer’s disease. The more we can understand subtype-specific differences in AD, the better we will be able to design rational therapeutic interventions to try to fix the problem that is primarily driving disease in each patient.” The researchers are continuing to study other pathways that may lead to Alzheimer’s disease, such as those involving microglia (brain cells that perform immune functions). By using study models and techniques reflective of Alzheimer’s disease presentation in the general population, the researchers hope to identify additional biological pathways important in Alzheimer’s disease. In addition, Brigham researchers have played a leadership role in understanding the molecular and genetic basis for Alzheimer’s disease, including making key discoveries related to the amyloid protein. Two novel anti-amyloid therapies, aducanumab and lecanemab, have received U.S. Food and Drug Administration accelerated and traditional approval, respectively, but not all patients respond to these drugs, warranting other treatment options. This work was supported by the National Institutes of Health (F31AG063399, U01AG072572, U01AG061356, RF1NS117446 and R01AG055909).

Study Unveils Shared Cellular Mechanisms in Major Dementias

Categories Brain & Behavior, Health

A griffon vulture — besties not pictured — in flight.

Like people, vultures have fewer friends as they age

Categories Earth, Energy & Environment, Life & Non-humans

UCLA researchers found Manuka honey significantly reduced tumor growth in mice with ER-positive breast cancer cells by 84% without affecting normal breast cells or causing major side effects.

Manuka Honey Shows Promise in Breast Cancer Treatment, UCLA Study Finds

Categories Health, Life & Non-humans

two women chatting

Venting to Friends: The Hidden Social Benefits and Potential Pitfalls

Categories Brain & Behavior, Social Sciences

UCLA Health's Semel Institute for Neuroscience and Human Behavior living lab will be home to psychedelic and Ecological Medicine research.

UCLA Transforms Rooftop into Groundbreaking Psychedelic Space

Categories Brain & Behavior

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Digital digs: Technology preserving Europe’s cultural heritage
New England water future mapped by UMass Amherst hydrologist: ‘Bigger Floods, Longer Droughts’
Ahead of COP29, WHO demands urgent integration of health in climate negotiations

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