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Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of tau aggregates. Research in animal models has generated hypotheses on the underlying mechanisms of the interaction between Aβ and tau pathology. In support of this interaction, results from clinical trials have shown that treatment with anti-Aβ monoclonal antibodies (mAbs) affects tau pathology.
View Article and Find Full Text PDFLecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils, was formally evaluated as a treatment for early Alzheimer's disease in a phase 2 study (Study 201) and the phase 3 Clarity AD study. These trials both included an 18-month, randomized study (core) and an open-label extension (OLE) phase where eligible participants received open-label lecanemab for up to 30 months to date. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL), biomarker (PET, Aβ42/40 ratio, and ptau181) and safety outcomes were evaluated.
View Article and Find Full Text PDFProgesterone receptors regulate susceptibility to spreading depression.
Exp Neurol
January 2025
Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; UVA Brain Institute, University of Virginia, Charlottesville, VA 22908, USA.
Migraine patients often experience sensory symptoms called auras accompanying the headaches. Cortical spreading depression (CSD), a slow-propagating wave of neuroglial depolarization followed by hyperpolarization is proposed to be the neurological mechanism underlying these auras. We have previously found that progesterone regulates susceptibility to migraine through progesterone receptor (PR) activation.
View Article and Find Full Text PDFWeakened Airway Epithelial Junctions and Enhanced Neutrophil Elastase Release Contribute to Age-Dependent Bacteremia Risk Following Pneumococcal Pneumonia.
Aging Cell
January 2025
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Streptococcus pneumoniae (Sp; pneumococcus), the most common agent of community-acquired pneumonia, can spread systemically, particularly in the elderly, highlighting the need for adjunctive therapies. The airway epithelial barrier defends against bacteremia and is dependent upon apical junctional complex (AJC) proteins such as E-cadherin. After mouse lung challenge, pneumolysin (PLY), a key Sp virulence factor, stimulates epithelial secretion of an inflammatory eicosanoid, triggering the infiltration of polymorphonuclear leukocytes (PMNs) that secrete high levels of neutrophil elastase (NE), thus promoting epithelial damage and systemic infection.
View Article and Find Full Text PDFThe Impact of Administrative Districts and Urban Landscape on the Dispersal of Aedes aegypti via Genetic Differentiation.
Mol Ecol
January 2025
Institute of Ecology and Evolutionary Biology, National Taiwan University, Taipei, Taiwan.
Mosquito-borne diseases affect millions and cause numerous deaths annually. Effective vector control, which hinges on understanding their dispersal, is vital for reducing infection rates. Given the variability in study results, likely due to environmental and human factors, gathering local dispersal data is critical for targeted disease control.
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