Documents in Process

It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD), both of which are genetic forms of Alzheimer's disease (AD).We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. [...]

The molecular mechanisms driving splenomegaly in myeloproliferative neoplasms (MPNs) remain poorly understood. Utilizing the Jak2-V617F knock-in mouse model, we investigated the role of β1- and β2-integrins in regulating spleen volume and spleen weight. [...]

Immune checkpoint inhibition has shown promising results in malignant melanoma, but not all patients respond equally well, necessitating early, accurate monitoring of immunotherapy response. [18F]FDG-PET/CT aids in characterising therapy response beyond morphology, but validated imaging biomarkers for immunotherapy response remain scarce. [...]

The European Medicines Agency has recommended testing for the ApoE-genotype prior to treatment of Alzheimer's disease with Lecanemab. The drug approval is limited to patients who are not homozygous for the ApoE epsilon 4 allele. [...]

Twinkle, encoded by the TWNK gene, is a mitochondrial DNA helicase that unwinds the double helix of DNA during replication, playing a pivotal role in mitochondrial function. Twinkle-related disorders encompass a variety of genetic disorders characterized by mitochondrial dysfunction. [...]

A specific and accurate blood test for acute brain injury could help monitor infarct growth in ischemic stroke and serve as a surrogate end point in clinical trials. Using a single-molecule detection assay, we assessed plasma brain-derived tau (BD-tau), a marker selectively quantifying tau protein from the central nervous system, in a prospective cohort of 502 patients with acute ischemic stroke with serial blood sampling from admission to day 7. [...]

Spinocerebellar ataxia type 3 (SCA3) is characterised by progressive brain atrophy, with regional volume loss detectable via MRI prior to clinical manifestation. We aimed to identify the previously unknown sequence of brain atrophy in SCA3 and evaluate whether this sequence can be translated into an atrophy staging framework to enable accurate clinical prognosis and trial enrichment.We included data from 322 SCA3 mutation carriers, enrolled in observational studies conducted across Europe, the Americas, and Asia. [...]

The Golgi apparatus is the central hub of secretory and endosomal pathways in a eukaryotic cell. Despite having a conserved basic organization, the Golgi varies greatly in structure and operation mode between different cell types, ranging from dispersed cisternae in the budding yeast to the ribbon of cisternae stacks in most mammalian cells. [...]

The β-secretase BACE1 (β-site amyloid precursor (APP) cleaving enzyme 1) is a major drug target for Alzheimer's disease (AD), as it catalyzes the first step in amyloid β (Aβ) generation, but has additional substrates and functions, in particular in the brain. Several advanced clinical trials with BACE1 inhibitors were stopped because of an adverse event, a mild cognitive worsening. [...]

Spatial biology has emerged as a pivotal area in many life science fields, with mass spectrometry imaging (MSI) becoming a cornerstone for molecular imaging. Among recent advancements to increase sensitivity, MALDI-2 technology has significantly expanded the molecular space accessible to MSI, increasing the ion yields of neutral metabolites, such as sterols. [...]