Multifunctional Liposomes Targeting Amyloid-ß Oligomers for Early Diagnosis and Therapy of Alzheimer's Disease.

Early detection and treatment are crucial for Alzheimer's disease (AD) management. Current diagnostic and therapeutic methods focus on late-stage amyloid fibrils and plaques, overlooking toxic soluble amyloid ß oligomers (AßOs) accumulating early in AD. A multifunctional liposome-based platform is designed for early diagnosis and therapy of AD, leveraging a novel self-assembled cyclic d,l-α-peptide (CP-2) that selectively targets AßOs. Biocompatible CP-2 conjugated liposomes (CP-2-LPs) effectively disrupt Aß aggregation and mitigate Aß-mediated toxicity in human neuroblastoma cells. In transgenic Caenorhabditis elegans AD models, CP-2-LPs significantly outperformed free CP-2 by improving cognitive and behavioral functions, extending lifespan, and reducing toxic AßO levels. Intravenous injection of fluorescently labeled CP-2-LPs reveals effective blood-brain barrier penetration, with significantly higher brain fluorescence in transgenic mice than WT, enabling precise diagnosis. These findings underscore CP-2-LPs as a valuable tool for early detection and targeted therapy in AD.

Overall survival of adult acute myeloid leukemia based on cytogenetic and molecular abnormalities during 5 years in a single center study.

OBJECTIVES: To determined the 5-year overall survival (OS) rates for adult patients with acute myeloid leukemia (AML) patients at King Abdulaziz Medical City, Jeddah, Saudi Arabia, based on cytogenetic and molecular abnormalities. Methods:  A retrospective cohort study reviewing adult AML patient files between 2011 and 2018. Sixty-three patients were excluded due to pediatric age and secondary AML. The remaining 87 adult patients with de novo AML were enrolled in this study. RESULTS: The most frequent cytogenetic abnormalities were t(15;17) (17.2%), followed by complex cytogenetic (13.8%) and t(8;21) (5.7%). The most frequent molecular abnormalities were promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) (16.1%) and Nucleophosmin 1 (NPM1) (11.5%). The highest OS rate was associated with t(15;17), PML-RARA, and NPM. However, complex cytogenetic was associated with the lowest OS rate; fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication was independently correlated with low OS rate. Conclusion: The study describes cytogenetic and molecular abnormalities observed in adult AML patients and gives an overview of prognostic factors and determine the OS, with comparable results with recent published data by the WHO.