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| http://dx.doi.org/10.1080/21505594.2017.1368942 | DOI Listing |
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Background: The key advantage of active immunization is the induction of sustained, polyclonal antibody responses that are readily boosted by occasional immunizations. Recent clinical trial outcomes for monoclonal antibodies lecanemab and donanemab, establish the relevance of targeting pathological Abeta for clearing amyloid plaques in Alzheimer's disease. ACI-24.
View Article and Find Full Text PDFBackground: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFSex-related differences in the morphology of rectal mucosa-associated lymphoid tissues in C57BL/6NCrSlc mice.
Histol Histopathol
December 2024
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Sex hormones regulate gut function and mucosal immunity; however, their specific effects on the mucosa-associated lymphoid tissue (MALT) in the rectum of mammals remain unclear. Here, we aimed to investigate the influence of sex on MALT in the rectum of mammals by focusing on the rectal mucosa-associated lymphoid tissues (RMALTs) of C57BL/6NCrSIc mice. Histological analysis revealed that RMALTs were predominantly located in the lamina propria and submucosa of the rectal mucosa, with a significant sex-related difference in the distance from the anorectal junction to the first appearance of the RMALT.
View Article and Find Full Text PDFBackground: Neuroinflammation is a critical factor of Alzheimer's Disease (AD). Dysregulation of complement leads to excessive inflammation, direct damage to self-cells and propagation of injury. This is likely of particular relevance in the brain where inflammation is poorly tolerated and brain cells are vulnerable to direct damage by complement.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Women account for almost two-thirds of Alzheimer's disease (AD) cases, yet evidence significantly less clinical benefit from recently deployed amyloid-lowering therapies. To close this disparity gap, there is an urgent need to identify biological drivers of sex differences in the manifestation and clinical response to AD therapeutics. A recent review of multi-omic studies of AD reported >75% of studies showed female-specific changes at the molecular level (vs.
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