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Advanced MRI techniques may provide non-invasive insight into the molecular heterogeneity of glioblastoma. Amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI reflects endogenous protein and peptide content, but its clinical and molecular correlates in therapy-naive glioblastoma, IDH-wildtype, remain incompletely understood.This retrospective single-center study included 53 adult patients with therapy-naive glioblastoma, IDH-wildtype, who underwent preoperative APTw MRI. [...]

Clinical proteomics is an evolving discipline that aims to identify new biomarker candidates of human disease to improve diagnosis, prognosis, treatment monitoring and the discovery of novel therapeutic targets. This article outlines the pathoproteomic characterization of dystrophinopathies, which are classified as muscle wasting diseases due to mutations in the DMD gene.The Special Report focuses on the proteomic profiling of progressive Duchenne muscular dystrophy of early childhood and more benign and later-onset Becker muscular dystrophy. [...]

Subtle symptoms, like subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD), can improve the risk stratification in preclinical Alzheimer´s disease (AD) but their importance is insufficiently elaborated.We pooled data from cognitively normal individuals participating in three longitudinal cohort studies (N = 13,192, 8,359[63.3%] female, mean [SD] age 71.0[8.4]).Compared to participants without SCD and MNPD (SCD-/MNPD-), SCD-/MNPD+, SCD+/MNPD-, and SCD+/MNPD+ participants had an increased risk for mild cognitive impairment (MCI) and dementia, including in amyloid-positive individuals. Focusing on SCD+/MNPD+ participants triples the positive predictive value of amyloid biomarker testing for the 5-year prediction of MCI and reduces the required samples size for trials in preclinical AD to one fourth, compared to considering all cognitively normal participants regardless of subtle symptoms.SCD and MNPD offer a powerful approach for risk stratification in preclinical AD, which can improve clinical trial designs, risk counseling, and future case identifications for early treatment..

Anti-IgLON5 disease is an autoimmune disease, in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction and Tau pathology. How α-IgLON5 AABs cause neuronal Tau protein pathology and neurodegeneration remains unclear. [...]

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex vivo investigations, the in vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. [...]

Left-right hippocampal volumetric asymmetry and atrophy are implicated in neurodegenerative and neuropsychiatric disorders, yet their molecular basis in healthy adults remains poorly understood.We conducted a meta-analysis of epigenome-wide association studies across six population-based cohorts (n = 8156; 53% women; mean age = 60.7 years) to identify DNA methylation signatures associated with left and right hippocampal volumes (LHCV, RHCV) and hippocampal asymmetry (i.e, differences between left and right volumes divided by their sums).We identified five CpGs and 262 differentially methylated regions associated with LHCV, nine CpGs and 246 regions with RHCV, one CpG and 16 regions with asymmetry. Cross-omics integration uncovered 15 LHCV-related and 13 RHCV-related methylation-gene expression pairs, with five overlapping genes primarily involved in immune regulation. [...]

Genetically encoded calcium (Ca2+) indicators (GECIs) are essential tools for monitoring neuronal activity, but the performance of red fluorescent GECIs has remained limited. In particular, many red indicators are relatively dim, produce low signal-to-noise ratios and can undergo unwanted photoswitching when exposed to blue light, restricting their use in all-optical experiments that combine imaging with optogenetics or multicolor imaging. [...]

The corpus callosum, the largest commissural structure in the human brain, is a central focus in research on aging and neurological diseases. It is also a critical target for interventions such as deep brain stimulation and serves as an important biomarker in clinical trials, including those investigating remyelination therapies. [...]

The role of inflammation in cortical superficial siderosis (cSS), a marker of cerebral amyloid angiopathy (CAA) linked to high hemorrhage risk, is unclear. We examined 15 patients with cSS using 3 T post-contrast vessel wall MRI (VWI) and CSF analysis. [...]