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Transthyretin amyloidosis (ATTR amyloidosis) is a rare systemic disorder characterized by the extracellular deposition of amyloid fibrils, which can affect multiple tissues. Lumbar spinal stenosis (LSS), a condition involving narrowing of the lumbar spinal canal, has been frequently associated with amyloid deposition in the ligamentum flavum (LF). This study aimed to evaluate the prevalence of ATTR deposits in LF samples obtained from patients undergoing LSS surgery at two Italian centers. A total of 37 patients were included, with LF thickness measured via pre-operative MRI scans. Amyloid deposits were detected in 27% of patients, all confirmed as ATTR by immunohistochemistry. DNA analysis revealed no pathogenic mutations in the TTR gene, suggesting that the detected amyloid fibrils originated from the wild-type protein. LF thickness values were consistent with those reported in literature, supporting LF thickening as a potential marker of amyloid deposition. These findings contribute to the understanding of ATTR involvement in LSS and highlight the need for further research to explore the pathophysiological mechanisms and clinical significance of amyloid deposits in the LF.
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http://dx.doi.org/10.1007/s10072-025-08101-1 | DOI Listing |
Pharmacol Ther
September 2025
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN 55902, USA; Department of Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USA.
Under physiological conditions, amyloid precursor protein (APP) is critically important for normal brain development, neurogenesis, neuronal survival, and synaptic signaling. Dyshomeostasis of APP increases deposition and accumulation of amyloid β (Aβ) in the brain parenchyma and cerebral blood vessels thereby leading to development of Alzheimer's disease and cerebral amyloid angiopathy. In this review, we critically examine existing literature supporting the concept that endothelial APP performs important vascular protective functions in the brain.
View Article and Find Full Text PDFJ Nucl Cardiol
August 2025
Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
Systemic amyloidosis is a complex disorder, making early and accurate diagnosis challenging. The most common types are associated with misfolded transthyretin or immunoglobulin light chains, where cardiac and renal amyloidosis portend the worst prognosis. Peptide p5+14 can bind all types of amyloid via multivalent electrostatic interactions.
View Article and Find Full Text PDFNat Commun
September 2025
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology).
View Article and Find Full Text PDFACS Chem Neurosci
September 2025
Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
The development of drugs for Alzheimer's disease, which accounts for over half of all dementia cases, remains challenging. Amyloid β 1-42 (Aβ42) is widely recognized for its deposition in the brains of patients with Alzheimer's disease. Furthermore, Aβ42-induced cell toxicity likely plays a role in disease onset.
View Article and Find Full Text PDFNeurosci Bull
September 2025
State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurotoxic amyloid beta (Aβ) deposition in the brain. Neurons can internalize and exocytose Aβ; however, the molecular pathways governing Aβ release remain poorly understood. To identify key regulators of Aβ42 transport, we applied formaldehyde cross-linking of protein complexes combined with co-immunoprecipitation and mass spectrometry analysis to identify TMED10 as a novel Aβ42-interacting protein.
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