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Current Progress and Future Directions in Non-Alzheimer's Disease Tau PET Tracers.
ACS Chem Neurosci
January 2025
Research Center for Accelerator and Radioisotope Science, Tohoku University, Sendai, Miyagi 980-0845, Japan.
Alzheimer's disease (AD) and non-AD tauopathies are dominant public health issues driven by several factors, especially in the aging population. The discovery of first-generation radiotracers, including [F]FDDNP, [C]PBB3, [F]flortaucipir, and the [F]THK series, for the in vivo detection of tauopathies has marked a significant breakthrough in the fields of neuroscience and radiopharmaceuticals, creating a robust new category of labeled compounds: tau positron emission tomography (PET) tracers. Subsequently, other tau PET tracers with improved binding properties have been developed using various chemical scaffolds to target the three-repeat/four-repeat (3R/4R) tau folds in AD.
View Article and Find Full Text PDFCellular Uptake of Tau Aggregates Triggers Disulfide Bond Formation in Four-Repeat Tau Monomers.
ACS Chem Neurosci
January 2025
Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80208, United States.
Oxidative stress is an important driver of aging and has been linked to numerous neurodegenerative disorders, including Alzheimer's disease. A key pathological hallmark of Alzheimer's are filamentous inclusions made of the microtubule associated protein Tau. Based on alternative splicing, Tau protein can feature either three or four microtubule binding repeats.
View Article and Find Full Text PDFPost-mortem neuropathology of idiopathic rapid eye movement sleep behaviour disorder: a case series.
Lancet Neurol
December 2024
Neurological Tissue Bank of the Biobank, FRCB-IDIBAPS, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain; Department of Pathology, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Article Synopsis
- The study examines post-mortem brain tissues from individuals diagnosed with idiopathic REM sleep behavior disorder (IRBD) to investigate its potential link to neurodegenerative diseases, specifically focusing on signs of neuronal loss and the presence of key protein deposits.
- Researchers analyzed samples from 20 participants, most of whom were diagnosed with Lewy body disease, while a small number had Parkinson's disease-related conditions, revealing significant findings of neuronal damage associated with α-synuclein proteins, particularly in brain regions controlling REM sleep.
- While the sample size limited the statistical analysis, the outcomes suggest a strong correlation between IRBD and neurodegenerative diseases, emphasizing the importance of these pathological features for understanding the progression
Pathological study of progressive supranuclear palsy the cases with mutations in Bassoon.
Neuropathology
October 2024
Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.
View Article and Find Full Text PDFLegumain/asparaginyl endopeptidase-resistant tau fibril fold produces corticobasal degeneration-specific C-terminal tau fragment.
Neurobiol Dis
October 2024
Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address:
Corticobasal degeneration (CBD) is a major four-repeat tauopathy along with progressive supranuclear palsy (PSP). Although detergent-insoluble 37-40-kDa carboxyl-terminal tau fragments (CTFs) are hallmarks of CBD pathology, the process of their formation is unknown. This study monitored the formation of CBD-type fibrils that exhibit astrocytic plaques, a characteristic CBD pathology, using its biochemical properties different from those of Alzheimer's disease/PSP-type fibrils.
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