Alzheimer's disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model the genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the gene encoding the amyloid precursor protein. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.
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http://dx.doi.org/10.3390/biomedicines12061193 | DOI Listing |
Metab Brain Dis
January 2025
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.
View Article and Find Full Text PDFInflammopharmacology
January 2025
Department of Pharmacology, Central University of Punjab, Bathinda, 151001, Punjab, India.
Alzheimer's Disease (AD), a progressive and age-associated neurodegenerative disorder, is primarily characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. Despite advances in targeting Aβ-mediated neuronal damage with anti-Aβ antibodies, these treatments provide only symptomatic relief and fail to address the multifactorial pathology of the disease. This necessitates the exploration of novel therapeutic approaches and a deeper understanding of molecular signaling mechanisms underlying AD.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Introduction: Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted.
Methods: Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS.
Alzheimers Dement
January 2025
Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
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