Background & aim: Efficient delivery of anti-β-amyloid (Aβ) antibodies across the blood–brain barrier (BBB) remains a central challenge in Alzheimer’s disease (AD) therapy. Therapeutic Aβ-targeted antibodies engineered for receptor-mediated transcytosis display improved brain exposure and therapeutic efficacy, yet their brain-wide…
Background & aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1RA effects on neuroinflammation remain poorly…
Background & aim: Central regulation of appetite and satiety engages neuronal populations distributed across the brain. The identification of novel drug targets, development of anti-obesity therapeutics, and validation of their mode of action benefit from whole-brain imaging. Light-sheet fluorescence…
Background & aim: Neurodegenerative diseases are characterized by complex, large-scale structural and cellular alterations across the brain. Understanding these changes requires comprehensive, whole-brain analysis at high spatial resolution. Three-dimensional light sheet fluorescence microscopy (3D LSFM) enables rapid imaging of intact…
Background & aim: Alzheimer’s disease (AD) is histologically defined by accumulation of Abeta (Ab) plaques in the brain. Age and gender are important factors in AD pathology. To develop more effective interventions, preclinical studies should therefore consider these factors in…
Background & aim: Progressive spreading of pathological alpha‑synuclein (αSyn) aggregates in the brain drives the degeneration of tyrosine hydroxylase (TH)-positive dopaminergic neurons in Parkinson’s disease (PD). Development of disease-modifying therapies has been hampered by the lack of techniques that can…
Background & aim: Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. In this study, we investigated brain delivery and effects on plaque burden of…
Background & aim: Tumor necrosis factor (TNF) is highly upregulated after ischemic stroke and plays a crucial role in shaping the neuroinflammatory response that follows. Therapies aimed at inhibiting detrimental soluble (sol)TNF-TNF receptor 1 (TNFR1) signaling are gaining interest as…
Background & aim: Nutrient-stimulated gut hormone peptide YY3e36 (PYY3e36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy…
Background & Aim: Alzheimer’s disease (AD) is histologically defined by accumulation of Abeta (Aβ) plaques in the brain. Age and gender are important factors in AD pathology. To develop more effective interventions, preclinical studies should therefore consider these factors in…