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Nanotubes deliver mitochondria to T cells, supercharging the T cells to make them more effective in the fight against cancer. Image courtesy of Shiladitya Sengupta, BWH

Study finds ‘supercharging’ T cells with mitochondria enhances their antitumor activity

Categories Brain & Behavior, Health

Cells containing tau aggregates (green) before (left) and 13 hours after treatment with RING-nanobody (right)

Therapy targets and destroys tau tangles in Alzheimer’s treatment

Categories Brain & Behavior, Health

Researchers have formed a consortium called SSPsyGene with the shared objective of studying the genetic causes of neurodevelopmental and psychiatric disorders (NPD). Their focus is on 250 high-risk genes that may contribute to these conditions. In the project's initial phase, they tested 23 of these risk genes. The stem cell lines they generated from this research will be shared globally to aid other scientists in studying how these genes contribute to NPD.

Scientists aim to decode the genetic roots of mental illness on a large scale

Categories Brain & Behavior, Health

Demo of app being used

Smartphone App Transforms Blood Pressure Monitoring for Underserved Communities

Categories Health, Technology

Couple walking on road

Lifestyle Advice: A Questionable Approach to Public Health

Categories Health

Vector art of two women sitting in a couch smiling

Cannabis Use Among Older Adults: New Study Reveals Surprising Trends and Risks

Categories Brain & Behavior, Health, Social Sciences

Baby drinking from bottle

Newborn Metabolic Patterns May Help Predict SIDS Risk, Study Finds

Categories Health

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

Figure 4. Effect of 2-BP treatment on senescence markers. Levels of p-p53 (A), HMGB1 (B), and lamin B1 (C) were measured in cell extracts from VSMCs. Cells were either pretreated with 2-BP for 24 hours before doxorubicin (DOX) treatment or treated with 2-BP alone for the specified durations. Protein levels were assessed using Western blotting, with representative blots shown (the red line indicates where the blot was cut) (D). Data are presented as means ± SEM from N=3 biological replicates. Statistical significance was determined using one-way ANOVA; *p

Protein Modification May Hold Key to Reversing Cellular Aging

Categories Health

Cartoon of a man's belly at the beach

Long-term exercisers have ‘healthier’ belly fat

Categories Health

Anti-nausea drug could help treat sleep apnea

Drug treatment shows promise for dangerous snoring condition, obstructive sleep apnea

Categories Health

New research from the University of Washington’s Institute for Learning & Brain Sciences, or I-LABS, found the COVID-19 pandemic lockdowns resulted in unusually accelerated brain maturation in adolescents. This maturation was more pronounced in females, as seen on the left.

COVID-19 Lockdowns Sped Up Brain Aging in Teens, Especially Girls

Categories Brain & Behavior, Health

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