Medical Bulletin 27/September/2025

For decades, Alzheimer’s research focused mainly on plaques and tangles of misfolded proteins. But this new work, published in Immunity, points to fat metabolism as a hidden culprit. Microglia near amyloid plaques were found to contain twice as many fat droplets as normal cells—and cleared 40% less toxic protein.

To uncover this, researchers examined brain tissue from people with Alzheimer’s disease and used advanced imaging and biochemical analyses to track how microglia processed fat when exposed to amyloid plaques. They discovered that microglia closest to plaques accumulated abnormal fat droplets, driven by an overactive enzyme called DGAT2. Further experiments in animal models showed that when DGAT2 was blocked or degraded, microglia regained their ability to clear amyloid beta, boosting neuronal health.

Researchers’s team discovered that targeting this enzyme—either blocking its activity or promoting its breakdown—helped restore microglial function in Alzheimer’s models. That means the brain’s own immune system could fight disease again, something drug therapies aimed directly at plaques have failed to do.

The findings suggest a radical shift in how we think about Alzheimer’s: not just “protein plaques,” but “lipid plaques” may be at the heart of brain degeneration. If future therapies can rebalance fat metabolism inside brain cells, researchers believe it could open an entirely new path to preventing or even slowing the disease.

Reference: Prakash, Priya, Manchanda, Palak, Paouri, Evi, Bisht, Kanchan, Sharma, Kaushik, Rajpoot, Jitika; Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease; Immunity; 2025; doi: 10.1016/j.immuni.2025.04.029

Mango Consumption Linked to Improved Metabolic Health and Diabetes Prevention

Do you also think grabbing a low-sugar snack bar is always the healthier choice? Hold on before you open that packet, because new research says otherwise. A randomized controlled trial led by clinical nutrition researcher Raedeh Basiri, published in Foods, showed that whole fruits—even those naturally high in sugar like mango—may actually improve health outcomes for people at risk of diabetes.

Globally, over 500 million adults live with prediabetes, a condition where blood sugar levels are higher than normal but not yet in the diabetes range. To test how different foods affect this group, researchers designed the first long-term clinical trial comparing mangoes to low-sugar snacks.

Participants with prediabetes were randomly assigned into two groups: one group ate a fresh mango daily (about 32 grams of natural sugar), while the other consumed a low-sugar granola bar each day (around 11 grams of sugar). Over six months, scientists carefully tracked participants’ fasting glucose levels, insulin sensitivity, and body composition, using standard metabolic tests and body fat measurements.

The results were striking. Despite having nearly three times more sugar, daily mango consumption improved insulin sensitivity and blood glucose regulation. Even more surprising, the mango group showed a reduction in body fat compared to those who ate the low-sugar granola bar.

These findings challenge the common belief that all sugars are equally harmful. Researchers emphasized that it’s not just the amount of sugar, but how it is delivered. In whole fruits like mango, natural sugars are paired with fiber, vitamins, and bioactive compounds that processed snacks lack—making them a safer, and even protective, option against diabetes.

Reference: Basiri, R., et al. (2025). Daily Mango Intake Improves Glycemic and Body Composition Outcomes in Adults with Prediabetes: A Randomized Controlled Study. Foods. doi.org/10.3390/foods14172971

Alcohol Use Linked to Higher Dementia Risk Across All Consumption Levels

Want to enjoy a drink this weekend? Hold on before raising that glass, and listen. A major new study from the University of Oxford and published in the journal BMJ Evidence-Based Medicine has raised serious concerns by revealing that alcohol consumption—even light or moderate drinking—raises the risk of dementia, challenging the long-held belief that small amounts of alcohol might be safe or even beneficial for brain health.

The study tracked over 559,000 participants from the UK Biobank and US Million Veteran Program for 4 to 12 years. Researchers examined their alcohol intake and dementia development, using advanced genetic methods called Mendelian randomization to confirm causation, not just correlation. The results showed a steady increase in dementia risk with any amount of alcohol consumption. Even just one to three extra drinks per week increased dementia risk by about 15% compared to lighter drinkers.

Genetic factors also played a role. People with genes linked to alcohol dependence had a higher dementia risk, regardless of how much they drank. Doubling this genetic risk was associated with a 16% higher chance of dementia.

Why did previous studies suggest moderate drinking was safe or protective? Old studies often included biases, like grouping former heavy drinkers into the “non-drinker” category or not accounting for changes in drinking habits before dementia diagnosis. This new study’s methods minimised these errors, providing clearer evidence.

The takeaway: There may be no truly “safe” alcohol level for brain health. Public health guidelines that recommend up to 14 units per week might not protect against dementia. Experts now urge people to cut down and ideally avoid alcohol to protect memory and cognition.

Focus on brain-healthy habits: exercise regularly, eat well, stay socially active, and consult your doctor, especially as you age.

Reference: Topiwala A, Levey DF, Zhou H, et alAlcohol use and risk of dementia in diverse populations: evidence from cohort, case–control and Mendelian randomisation approachesBMJ Evidence-Based Medicine Published Online First: 23 September 2025. doi: 10.1136/bmjebm-2025-113913