Alzheimer’s disease is the most common form of dementia, which affects approximately 57 million people globally – a number that’s projected to rise to more than 150 million by 2050.
Category: neuroscience – Page 10
MicroRNA-based gene therapy to treat ALS
A single IV injection of a microRNA-based biologic suppressed production of the mutant SOD1 protein that causes amyotrophic lateral sclerosis (ALS); delayed disease onset by 60 days; and extended lifespan by 100 days, more than triple the average survival time, in mice models of the disease.
The gene therapy, delivered via adeno-associated virus (AAV) vector, preserved motor neurons and maintained neuromuscular connections in treated animals, which translated into improved muscle and respiratory function, motor performance, and lifespan in pre-clinical studies. These findings, published in Nature Communications, have the potential for clinical application in patients with SOD1-caused ALS, as well as other neurodegenerative diseases caused by toxic, gain-of-function gene mutations.
“These therapeutic benefits, from a single IV injection, are unprecedented among gene therapy approaches in this mouse model,” said the senior author. “No other studies have been able to achieve this kind of survival extension. This makes us very optimistic that our approach could have a meaningful impact for patients suffering from this horrible disease and warrants further clinical evaluation.”
Cerebral Edema in Traumatic Brain Injury
Cerebral edema is the abnormal accumulation of fluid in any of the tissue compartments of the cerebral parenchyma. It remains a significant challenge in neurotrauma care because it contributes to secondary brain injury, affecting prognosis. This review analyzes the recent literature, including foundational studies, to describe the mechanisms of distinct types of cerebral edema following traumatic brain injury (TBI). Emerging concepts, such as the role of the glymphatic system and heme-derived inflammasomes, offer new insights into new types of edemas, differentiated by pathogenesis and potential treatments. Recent advancements in understanding these molecular mechanisms can improve therapeutic strategies, facilitating a better approach in the era of precision and personalized medicine.
Should Brain MRI Screening Expand in Metastatic Breast Cancer?
Brain metastases are a major clinical concern in metastatic breast cancer, particularly in HER2-positive and triple-negative disease. Over time, approximately 25% to 50% of patients with these subtypes develop brain metastases, which can lead to neurological disability, cognitive impairment, reduced independence, and substantial deterioration in quality of life.
Despite this risk, routine brain imaging is not consistently recommended for patients without neurological symptoms.
An article published in The Breast argues that it may be time to reconsider this symptom-directed approach. Sarah Sammons, Nayan Lamba, and Nancy U. Lin outline a growing case for brain MRI screening in selected patients with metastatic breast cancer, while also acknowledging that survival benefit, optimal timing, cost-effectiveness, and potential harms remain uncertain.
Combination of Radiotherapy and Immunotherapy in Advanced NonSmall Cell Lung Cancer
Cerebral edema is the abnormal accumulation of fluid in any of the tissue compartments of the cerebral parenchyma. It remains a significant challenge in neurotrauma care because it contributes to secondary brain injury, affecting prognosis. This review analyzes the recent literature, including foundational studies, to describe the mechanisms of distinct types of cerebral edema following traumatic brain injury (TBI). Emerging concepts, such as the role of the glymphatic system and heme-derived inflammasomes, offer new insights into new types of edemas, differentiated by pathogenesis and potential treatments. Recent advancements in understanding these molecular mechanisms can improve therapeutic strategies, facilitating a better approach in the era of precision and personalized medicine. Although there has been notable progress, a proposal to customize treatments for diverse types of edemas is necessary to improve outcomes following traumatic brain injury. In this review, we describe the current subtypes of post-traumatic brain edemas and link them to a specific management approach.
Stereotactic Radiotherapy vs HippocampalAvoidance Whole Brain Radiation
As patients live longer with advanced cancer, brain metastases are now becoming a frequent and even chronic condition managed with a variety of systemic agents and local treatments.1 Radiotherapy plays a key role in treatment of intracranial lesions. Whole brain radiation therapy (WBRT) has the benefit of treating both imaging-apparent and microscopic disease. This approach can offer general intracranial disease control, but can damage healthy brain tissue, resulting in neurocognitive impairment associated with irradiation of the hippocampus.2 The innovation of hippocampal-avoidance WBRT (HA-WBRT) maintains global intracranial disease control while reducing neurocognitive decline relative to traditional WBRT, even in the setting of the neuroprotectant memantine (0.74; 95% CI, 0.58−0.95; P = .02), making HA-WBRT a standard-of-care approach to appropriate patients.3-5 Nevertheless, HA-WBRT requires several weeks of daily treatments and often time off systemic therapy. Conversely, stereotactic radiation (SRT) is given over 1 to 3 treatments to the visible lesions, allowing for higher radiation dose, better focal disease control, and sparing of healthy brain tissue, which further reduces neurocognitive toxic effects. SRT is appropriate for patients with a finite number of visible lesions but may allow microscopic disease elsewhere in the brain to progress, necessitating subsequent treatments or even salvage WBRT. In addition, the higher dose of SRT can cause radiation necrosis and inflammation, requiring steroids or other medical and surgical interventions.4 The optimal balance of intracranial disease control with patient-reported outcomes (PROs) is of increasing importance as patients live longer with the subacute and chronic toxic effects of radiotherapy.
To find that balance, multiple randomized clinical trials have confirmed that SRT offers improved efficacy and PROs compared with WBRT in patients with 1 to 4 brain metastases.2, 6-9 However, with advances in systemic therapy and surveillance, patients now frequently present with multiple brain metastases, high performance status, and expected survival of months to years. Without any high-level evidence comparing the efficacy and toxic effects of HA-WBRT with SRT in patients with 5 or more brain metastases, radiation oncologists have been left to make recommendations between each modality on a case-by-case basis. Shared decision-making attempts to account for lesion number, velocity, distribution, size, histologic findings, symptomatology, available systemic therapeutics with central nervous system penetrance, treatment goals, and tolerance for cognitive decline.
Daytime cortisol patterns track cognitive decline but not Alzheimer’s disease risk
In 3,895 older adults, moderate daytime cortisol variability was associated with better cognition and slower decline, while the highest daily cortisol exposure was linked to poorer cognition and faster decline. Cortisol patterns differed between Black and White participants, but their relationships with cognition were similar, and none predicted incident Alzheimer’s disease.
Comorbidities and Outcomes in People with Functional Neurological Disorder
In this cohort study, we retrospectively analyzed a large FND cohort using TriNetX, a federated health research platform aggregating electronic health records from approximately 160 million individuals across 143 health care organizations in 17 countries. Diagnoses follow standardized clinical coding. Reporting adhered to the STROBE guideline. This study was exempt from IRB review and informed consent given the use of deidentified data, according to the Common Rule (45 CFR §46) and UK regulations from the Health Research Authority.
Demographics and lifetime comorbidities were extracted for patients with an initial F44.4-F44.7 diagnosis between 1995 and 2024. Clinical outcomes were compared between matched cohorts with an initial diagnosis between 2015 and 2024 to reflect contemporary care for all FND vs multiple sclerosis (MS; G35), FND-motor vs MS, and FND-seizure vs epilepsy (G40), controlling for age, sex, race, and ethnicity via propensity score matching, testing 2-sided z tests on absolute risk differences at a significance level of P .05 after Bonferroni correction for multiple comparisons, and calculating odds ratios with 95% CIs. Data extraction and analyses were performed in April 2025 on the web-based interface TriNetX LIVE. Full methods are described in eMethods 1 to 3 in Supplement 1.
Targeting EpsteinBarr virus (EBV) for treatment of multiple sclerosis
Epstein-Barr Virus (EBV) is now recognized as an essential causal agent in the development of Multiple Sclerosis (MS). MS is a chronic autoimmune disease resulting in demyelination and neurodegeneration in the central nervous system (CNS). EBV is a ubiquitous human γ-herpesvirus that establishes long-term latent infection in a small subpopulation of memory B-lymphocytes. While EBV and B-lymphocytes are known to be drivers of MS autoimmune disease, it remains enigmatic how a small population of EBV-infected cells trigger and drive MS pathogenesis in some individuals. In this review, we discuss the known biology of EBV and its role in MS and other disease, including cancers, where EBV is an essential driving factor in disease progression. We review some of the conditions and cofactors that increase the risk of EBV infection leading to MS and the potential of pharmacological, biologic and vaccine approaches to more selectively target EBV to treat MS.
Keywords: EBNA1; Episome; Latency; Multiple Sclerosis; Therapeutics.
Copyright © 2026. Published by Elsevier B.V.