12/29/2023 0 Comments Igor 2008 video game roger l jacksonIndeed, huCSF Aβ is being developed as a primary biological marker of preclinical and clinical AD ( Shaw et al., 2007), but the question of its pathophysiological activity and the effects of immunotherapy on any such activity has not been elucidated. One such source is human CSF (huCSF), which is known to contain many different Aβ species, including low- n oligomers of variable length ( Walsh et al., 2000). Given the lability of Aβ conformation it is important to evaluate the peptide in its native state. Because the biological activity of Aβ oligomers and the ability to target them selectively with immunotherapy is critically dependent on their conformation, it is of great interest to compare animal- and human-derived Aβ oligomers. Animal cell-derived Aβ oligomers are extremely potent at disrupting cognition and synaptic plasticity ( Walsh et al., 2002 Cleary et al., 2005 Townsend et al., 2006). In the biosynthesis of Aβ, many different lengths and conformations of the peptide are generated, including highly mobile soluble Aβ oligomers, which are believed to mediate the earliest stages of AD ( Klein et al., 2001). Although endogenously generated and exogenously applied antibodies to Aβ can reduce cognitive and synaptic plasticity deficits in amyloid precursor protein (APP)-related transgenic mice ( Janus et al., 2000 Dodart et al., 2002 Kotilinek et al., 2002) and Aβ infusion models ( Klyubin et al., 2005), it is unclear whether animal cell-generated human Aβ behaves in a manner similar to human-derived Aβ. Studies of the clinical efficacy of active immunization against preaggregated Aβ and passive immunization with anti-Aβ antibodies have commenced in humans ( Gilman et al., 2005 Solomon, 2007) based primarily on studies of animal models that over-express Aβ ( Schenk et al., 1999 Bard et al., 2000). Immunotherapy targeting Aβ offers a potential disease modifying treatment for Alzheimer's disease (AD) ( Roberson and Mucke, 2006).
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