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Background: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFDementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
Siemens Heathineers, Princeton, NJ, USA.
Background: The recent breakthrough in monoclonal antibody treatment for Alzheimer's disease (AD) has ushered in a new phase in AD healthcare. However, associated amyloid-related imaging abnormalities (ARIA) present a significant risk to patients, necessitating careful monitoring. Detection by radiologists can be challenging and may suffer from inconsistency.
View Article and Find Full Text PDFA Rare and Intriguing Case of Wilson's Disease Initially Suspected of Systemic Lupus Erythematosus.
Clin Case Rep
January 2025
Rheumatic Diseases Research Center, Ghaem Hospital, Taghi Abad Mashhad University of Medical Sciences Mashhad Iran.
When systematic lupus erythematosus-like lab results (e.g., positive anti-double-stranded DNA antibody, low complement component 3) are inconsistent with physical findings, such as the absence of arthritis or nephritis, clinicians should consider diagnoses such as Wilson's disease, especially in the presence of abnormal liver function and elevated international normalized ratio (INR).
View Article and Find Full Text PDFEvaluating the Synergistic Effects of Multi-Epitope Nanobodies on BA.2.86 Variant Immune Escape.
J Phys Chem Lett
January 2025
School of Physics and Electronics, Shandong Normal University, Jinan 250014, China.
Addressing the frequent emergence of SARS-CoV-2 mutant strains requires therapeutic approaches with innovative neutralization mechanisms. The targeting of multivalent nanobodies can enhance potency and reduce the risk of viral escape, positioning them as promising drug candidates. Here, the synergistic mechanisms of the two types of nanobodies are investigated deeply.
View Article and Find Full Text PDFBackground: Initial analysis of liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov; unique identifier NCT03193151) using rejection-associated transcripts failed to find an antibody-mediated rejection state (ie, rich in natural killer [NK] cells and with interferon-gamma effects). We recently developed an optimization strategy in lung transplants that isolated an NK cell-enriched rejection-like (NKRL) state that was molecularly distinct from T cell-mediated rejection (TCMR).
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