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Advancing Early Detection of Alzheimer Disease in the Primary Care Setting in the United States

Background and ObjectivesAs evidence supporting the robustness of blood-based biomarker (BBM) testing for Alzheimer disease (AD) continues to emerge, understanding the perceptions, drivers, and barriers to the adoption of these tests among primary care…

Use of Ictal-Interictal SPECT in Localization of Surface-EEG–Negative Insular Epilepsy

This case demonstrates the use of ictal SPECT as an objective way to localize surface-EEG–negative insular seizures.


A 43-year-old woman presented with events characterized by a “funny” feeling in the head, nausea, and right-hand numbness/cramping. Events lasted minutes, without impaired awareness. Onset occurred 1.5 years after an embolic left middle cerebral artery stroke. MRI showed left temporoparietal and insular T2 changes.

Synchrotron‐generated microbeams as a radiosurgical alternative for drug‐resistant epilepsies: Proof of concept in a mouse model of mesiotemporal lobe epilepsy

“This proof-of-concept study highlights MRT as a promising non-invasive therapy for drug-resistant focal epilepsies with optimal peak doses of 125–250 Gy, and it suggests that distributing the dose through multiple angles optimizes the therapeutic effect. MRT could provide a safer alternative to surgery, warranting further investigations.”

Read this open-access research article from Epilepsia Journal at doi.org/10.1002/epi.70063.


Objective One-third of patients with epilepsy, particularly those with mesial temporal lobe epilepsy (MTLE), remain resistant to medication. Resective surgery, the gold standard, is highly invasive and carries significant risks. Here, using a mouse model, we explored the potential of microbeam radiation therapy (MRT), a new technique based on the spatial microfractionation of high-flux X-rays, as a non-invasive alternative for treating MTLE.

Cyanobacteria can utilize toxic guanidine as a nitrogen source

Guanidine is an organic compound primarily used as a denaturing reagent to disrupt the structures of proteins and nucleic acids. Together with partner institutions, scientists at the Helmholtz Centre for Environmental Research (UFZ) have demonstrated that cyanobacteria, which play a central role in global biogeochemical cycles, use guanidine as a nitrogen source.

The results were recently published in the Proceedings of the National Academy of Sciences. The researchers shed light on the underlying mechanisms and the potential for a new tool for sustainable biotechnological applications.

Scientists Discover Method To Erase Toxic Tau From Human Neurons

Researchers at the University of New Mexico have uncovered an unexpected role for OTULIN, an enzyme best known for its involvement in immune system regulation. The team found that OTULIN also plays a key role in the production of tau, a protein linked to many neurodegenerative disorders, along with brain inflammation and the biological processes associated with aging.

The findings were reported in the journal Genomic Psychiatry. In the study, scientists showed that disabling OTULIN stopped tau from being produced and cleared existing tau from neurons. This was achieved in two ways: by using a specially designed small molecule or by removing the gene responsible for producing the enzyme. The experiments were carried out in two types of cells, including cells derived from a person who had died from late-onset sporadic Alzheimer’s disease and human neuroblastoma cells that are commonly used in laboratory research.

Surprise Hair Loss Breakthrough: A DNA Sugar Gel Sparks Robust Regrowth

In 2024, scientists stumbled upon a potential new treatment for hereditary-patterned baldness, the most common cause of hair loss in both men and women worldwide.

It began with research on a naturally occurring sugar that helps form DNA: the ‘deoxyribose’ part of deoxyribonucleic acid.

While studying how these sugars aid wound healing in mice when applied topically, scientists at the University of Sheffield and COMSATS University in Pakistan noticed that the fur around treated lesions grew back faster than in untreated mice.

Complement C4d Informs the Differential Diagnosis of Inflammatory Demyelinating CNS Diseases

C4d is a sensitive marker for identifying antibody-related lesion pathology, enabling differentiation of idiopathic inflammatory demyelinating diseases in tissues and distinguishing both seropositive and seronegative NMOSD from multiple sclerosis in CSF.


Background and Objectives.

Lifespan‐Extending Endogenous Metabolites

Endogenous metabolites are small molecules produced by an organism’s own metabolism. They encompass a wide range of molecules, such as amino acids, lipids, nucleotides, and sugars, which are pivotal for cellular function and organismal health (Baker and Rutter 2023). Beyond serving as biosynthetic precursors and energy substrates, many metabolites also function as dynamic modulators of signaling and gene regulatory networks by engaging in protein–metabolite interactions, allosteric regulation, and by serving as substrates for chromatin and other post-translational modifications (Boon et al. 2020 ; Hornisch and Piazza 2025). Metabolites can function as extracellular signals activating G protein-coupled receptors (GPCRs), such as free fatty acid receptors for fatty acids, GPR81 for lactate, SUCNR1 for succinate, and TGR5 for bile acids (Tonack et al. 2013). These GPCRs are expressed in gut, adipose tissue, endocrine glands, and immune cells, linking nutrient and metabolite levels to diverse physiological responses (Tonack et al. 2013). Other metabolites serve as enzyme cofactors or epigenetic regulators. For example, methyl donors like betaine provide methyl groups for DNA and histone methylation and also act as osmolytes to protect cells under stress (Lever and Slow 2010). Some metabolites even form specialized structural assemblies. For instance, guanine crystals can form structural color in feline eyes and contribute to enhanced night vision (Aizen et al. 2018).

Perturbations of endogenous metabolite levels or fluxes have been linked to genomic instability, metabolic dysfunction, and age-related diseases, motivating study of metabolites as both biomarkers and functional modulators of aging (Adav and Wang 2021 ; Tomar and Erber 2023 ; Xiao et al. 2025). Metabolomic studies reveal characteristic metabolite changes in diabetes, cardiovascular disease, and Alzheimer’s disease (AD) (Panyard et al. 2022), suggesting that metabolites not only reflect organismal state but also can actively influence aging pathways. In subsequent sections, we will examine specific endogenous metabolites implicated in longevity regulation.

Atypical intraductal proliferation in prostate biopsy — a diagnostic grey zone with clinical implications

Atypical intraductal proliferation is a prostate biopsy finding with morphological features intermediate between high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. This Review discusses histopathological features, molecular characteristics and clinical outcomes associated with AIP, and highlights the clinical implications of AIP, primarily due to the frequent association of AIP with clinically significant prostate cancer.

Disrupting HDAC1 condensates in glioblastoma could help to overcome drug resistance

Glioblastoma (GBM) is one of the most common and aggressive primary brain tumors in adults, carrying an extremely poor prognosis and a median overall survival typically less than two years. Temozolomide (TMZ) is currently the only chemotherapeutic agent widely used in clinical practice. However, around 90% of cases experience tumor recurrence due to acquired resistance. How to overcome TMZ resistance remains a challenge.

In a study published in Nature Chemical Biology, Dr. Dong Peng’s team from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and collaborators from Sun Yat-sen University have discovered that TMZ treatment induces the formation of HDAC1-CTCF condensates in GBM cells. The team identified the small-molecule compound resminostat as a therapeutic agent capable of targeting these condensates.

Through three-dimensional (3D) super-resolution imaging independently developed by Dr. Dong’s team, the researchers observed a significant reduction in chromatin accessibility in TMZ-resistant GBM cells. The team characterized their 3D genomic structural features, and revealed that the decreased chromatin accessibility in resistant cells is primarily attributed to TMZ-induced formation of HDAC1-CTCF condensates, which accumulate on chromatin and restrict local accessibility.

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