Among the challenges facing translational medicine today is the need for greater productivity and safety during the drug development process. To meet this need, practitioners of translational medicine are developing new technologies that can facilitate decision making during the early stages of drug discovery and clinical development. Ex Vivo Metrics is an emerging technology that addresses this need by using intact human organs ethically donated for research. After hypothermic storage, the organs are reanimated by blood perfusion, providing physiologically and biochemically stable preparations. In terms of emulating human exposure to drugs, Ex Vivo Metrics is the closest biological system available for clinical trials. Early application of this tool for evaluating drug targeting, efficacy, and toxicity could result in better selection among promising drug candidates, greater drug productivity, and increased safety.
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http://dx.doi.org/10.1186/1479-5876-6-5 | DOI Listing |
Alzheimers Dement
December 2024
Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Background: The 18F-AV-1451 radioligand enables in-vivo identification of tau neurofibrillary tangles that are considered as biomarkers of neurodegeneration in Alzheimer Disease (AD). However, off-target radioligand binding is also observed in basal ganglia, known as an iron-rich region. Hence, it is important to distinguish between radioligand-identified tissue neurodegeneration and iron-related radioligand binding effects.
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December 2024
LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
Background: In-vivo PET imaging studies have demonstrated neuroinflammation (microglia reactivity) in the neocortex of Alzheimer's disease (AD) patients. However, the extent and implication of microglia reactivity in white matter regions remains unclear. Here, we explored microglia reactivity in white matter using PET imaging of the translocator protein (TSPO) in relation to core AD biomarkers (amyloid, tau, and astrogliosis), microstructural damage, and cognitive decline.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Douglas Mental Health University Institute, Montreal, QC, Canada.
White matter hyperintensities (WMHs) are frequently observed in ageing individuals, and have a higher prevalence in neurodegenerative disorders such as Alzheimer's disease. Ex-vivo assessments of the microstructural alterations within WMHs have reported heterogeneous tissue alterations, with demyelination, axonal loss, and inflammation presenting with various degrees of severity. There is a crucial need to better assess the severity of WMH microstructural alterations in vivo, in particular with the emergence of anti-amyloid immunotherapies and the associated risk of Amyloid Related Imaging Abnormalities (ARIAs) in individuals with comorbid vascular disease.
View Article and Find Full Text PDFBackground: Myelin integrity is central to healthy brains and is increasingly shown to be compromised in neurodegenerative diseases. Diffusion- and susceptibility-based MRI metrics can detect myelin changes. We show advanced diffusion and susceptibility metrics can detect degenerative myelin changes in ex vivo AD and HD mouse models.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.
Background: The hippocampus and its subfields in the human brain play a pivotal role in forming new memories and spatial navigation. The automated assessment of the hippocampus and its subfields are useful tools for the early diagnosis of Alzheimer's disease and other neurodegenerative diseases such as primary age-related tauopathy, Lewy body dementia, limbic-predominant age-related TDP-43 encephalopathy (LATE), and frontotemporal lobar Dementia. Postmortem brain magnetic resonance imaging plays a crucial role in neuroscience and clinical research, providing valuable insights into the structural and pathological features of the brain after death.
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