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Depletion of nuclear cytoophidia in Alzheimer's disease.
Free Neuropathol
January 2025
Department of Laboratory Medicine, St. Michael's Hospital, Unity Health & Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
There is considerable evidence for a role for metabolic dysregulation, including disordered purine nucleotide metabolism, in the pathogenesis of Alzheimer's disease (AD). Purine nucleotide synthesis in the brain is regulated with high fidelity to co-ordinate supply with demand. The assembly of some purine biosynthetic enzymes into linear filamentous aggregates called "cytoophidia" (Gk.
View Article and Find Full Text PDFDistinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.
Brain Commun
February 2025
Centre for Medical Image Computing, Department of Computer Science, University College London, London WC1V 6LJ, UK.
Although the corticobasal syndrome was originally most closely linked with the pathology of corticobasal degeneration, the 2013 Armstrong clinical diagnostic criteria, without the addition of aetiology-specific biomarkers, have limited positive predictive value for identifying corticobasal degeneration pathology in life. Autopsy studies demonstrate considerable pathological heterogeneity in corticobasal syndrome, with corticobasal degeneration pathology accounting for only ∼50% of clinically diagnosed individuals. Individualized disease stage and progression modelling of brain changes in corticobasal syndrome may have utility in predicting this underlying pathological heterogeneity, and in turn improve the design of clinical trials for emerging disease-modifying therapies.
View Article and Find Full Text PDFStructure-Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1-indoles as Tauopathy Positron Emission Tomography Radiotracers.
J Med Chem
March 2025
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States.
Structure-activity relationship studies were performed on a library of synthesized compounds based on previously identified tau ligands. The top 13 new compounds had values in the range of 5-14 nM in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One of the more promising new compounds ([H]) bound with high affinity in AD, PSP, and CBD tissues ('s = 1-1.
View Article and Find Full Text PDFRadiosynthesis, Characterization, and PET Neuroimaging of [F]F-4 for Tau Protein: A First-in-Human PET Study.
ACS Chem Neurosci
March 2025
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, CAMH, Toronto M5T 1R8, Canada.
[F]PI-2620 is a promising radiopharmaceutical for positron emission tomography (PET) imaging of both Alzheimer's disease (AD) and non-Alzheimer's disease (non-AD) tauopathies in humans. An array of fluorinated derivatives of the carbazole scaffold of PI-2620 were synthesized and evaluated. binding assays with [H]PI-2620 in human tissues with AD, progressive supranuclear palsy, and corticobasal degeneration, combined with predictions of blood-brain barrier permeability, led to the selection and radiosynthesis of [F]F-4 as a promising radiotracer.
View Article and Find Full Text PDFUnmasking the Unexpected: FIG4-Related Disorder Presenting with Progressive Supranuclear Palsy-Like Features.
Mov Disord Clin Pract
March 2025
Department of Neurology, Rothschild Foundation Hospital, Paris, France.
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