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Automated cerebrospinal fluid (CSF) biomarker assays have largely replaced manual immunoassays for measuring amyloid pathology in CSF. We refitted and validated the ABIDE model, predicting progression from mild cognitive impairment (MCI) to dementia, with CSF measurements from the automated Elecsys platform.We included 2413 MCI participants (998 [41%] amyloid-positive) from seven observational cohorts. [...]

DNA methylation-based classification is now central to contemporary neuro-oncology, as highlighted by the World Health Organization (WHO) classification of central nervous system (CNS) tumors. We present the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.8), trained on 7,495 methylation profiles, which expands recognized entities from 91 classes in version 11 (v11) to 184 subclasses. [...]

Aging is a key risk factor for disease in mammals, yet its molecular basis across organs remains unclear. Here, we performed bulk RNA sequencing on eight organs (brain, heart, kidney, liver, lung, skeletal muscle, spleen, testis) from male C57BL/6J mice at distinct life stages. [...]

Alzheimer's disease and coronary artery disease are common late-life chronic conditions and share multiple risk factors, including the apolipoprotein E (APOE) ε4 allele. A meta-analysis of two multidomain lifestyle intervention trials found greater cognitive benefits in APOE4 carriers compared with non-carriers. [...]

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of refractory hematological malignancies but is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS). Early clinical recognition remains challenging, as the commonly used Immune Effector Cell-Associated Encephalopathy (ICE) score lacks sensitivity for subtle deficits.In this prospective bicentric study, 100 patients treated with CAR T-cells at Hannover Medical School and Charité - Universitätsmedizin Berlin underwent systematic neurological assessments using both ICE and the newly developed Berlin-Hannover ICANS Severity Assessment (BHISA). [...]

Intramembrane proteolysis by γ-secretase is critically implicated in Alzheimer disease pathogenesis by processing of its amyloid precursor protein substrate C99 into harmful amyloid-β peptide (Aβ) species. Recruitment of C99 involves binding of its N-terminal extracellular domain to exosites in γ-secretase. [...]

Cerebral small vessel disease (SVD) is a common chronic cerebrovascular disorder with poorly understood pathomechanisms. Genetic studies have identified FOXF2 as a major risk gene for both SVD and stroke. [...]

Blood-brain barrier (BBB) integrity is critical for brain homeostasis, with malfunctions contributing to neurovascular and neurodegenerative disorders. Mechanistic studies on BBB function have been mostly conducted in rodent and in vitro models, which recapitulate some disease features, but have limited translatability to humans and pose challenges for drug discovery. [...]

Understanding the functional principles of the human brain requires deep insight into its neuronal and network physiology. In superficial layers of temporal cortex, molecular and morphological subtypes of glutamatergic excitatory pyramidal neurons have been described, but subtyping based on electrophysiological parameters has not been performed. [...]

Here we established an in vivo CRISPR screening pipeline using genetically editable progenitor cells to dissect macrophage regulation in mouse models of multiple sclerosis (MS). Screening over 100 cytokine receptors and signaling molecules identified interferon-γ, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and transforming growth factor-β as essential regulators of macrophage polarization in vivo. [...]