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Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.
Elife
September 2024
Center for Advanced Studies and Technology - CAST, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.
The recent, controversial approval of antibody-based treatments for Alzheimer's disease (AD) is fueling a heated debate on the molecular determinants of this condition. The discussion should also incorporate a critical revision of the limitations of preclinical mouse models in advancing our understanding of AD. We critically discuss the limitations of animal models, stressing the need for careful consideration of how experiments are designed and results interpreted.
View Article and Find Full Text PDFFeatures that characterize monoclonal light chain ("myeloma") cast nephropathy with immunofluorescence challenges and emphasis on electron microscopy.
Ultrastruct Pathol
September 2024
Department of Pathology and Interdisciplinary Clinical Oncology, University of South Alabama, Mobile, AL, USA.
Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasias. The serum-free light chain assay is used in patients, mostly older, with unexplained acute kidney injury to screen for potential myeloma cast nephropathy. This study consists of a systematic review of diagnostic features in myeloma cast nephropathy.
View Article and Find Full Text PDFSurface-catalyzed liquid-liquid phase separation and amyloid-like assembly in microscale compartments.
J Colloid Interface Sci
December 2024
Department of Physics and Chemistry - Emilio Segrè, University of Palermo, Viale delle Scienze, 18, 90128, Palermo, Italy. Electronic address:
Liquid-liquid phase separation is a key phenomenon in the formation of membrane-less structures within the cell, appearing as liquid biomolecular condensates. Protein condensates are the most studied for their biological relevance, and their tendency to evolve, resulting in the formation of aggregates with a high level of order called amyloid. In this study, it is demonstrated that Human Insulin forms micrometric, round amyloid-like structures at room temperature within sub-microliter scale aqueous compartments.
View Article and Find Full Text PDFDonanemab, another anti-Alzheimer's drug with risk and uncertain benefit.
Ageing Res Rev
August 2024
School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus Faculty of Medicine and Health, UNSW, Sydney, Australia; St Vincent's Hospital Centre for Applied Medical Research, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia. Electronic address:
Article Synopsis
- The FDA has approved two monoclonal antibodies, aducanumab and lecanemab, for reducing amyloid plaques in Alzheimer's patients, while a third, donanemab, is awaiting approval.
- The approvals suggest these drugs may delay cognitive decline, but the actual improvements are small and might be less effective than existing medications like cholinesterase inhibitors.
- Concerns arise about the potential misinterpretation of data and risks of tissue damage, leading to recommendations to pause approvals until these effects are fully understood to prevent harming patients.
Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?
Int J Mol Sci
March 2024
Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, LA 90095, USA.
Article Synopsis
- The amyloid cascade hypothesis, which suggests amyloid-beta causes Alzheimer's disease, is facing scrutiny despite ongoing support and recent antibody approvals.
- Aducanumab and lecanemab have been FDA-approved, with donanemab currently under review, based on the idea they remove amyloid deposits in the brain.
- However, concerns about the effectiveness of these treatments, issues with trial patient selection, and potential negative effects on the brain highlight the need for further research into the validity of the amyloid hypothesis.
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