A Seed for Alzheimer Amyloid in the Brain
Open Access
- 19 May 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (20) , 4894-4902
- https://doi.org/10.1523/jneurosci.0861-04.2004
Abstract
A fundamental question about the early pathogenesis of Alzheimer's disease (AD) concerns how toxic aggregates of amyloid β protein (Aβ) are formed from its nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound Aβ (GAβ) is involved in the process. We now examined this possibility using a novel monoclonal antibody raised against GAβ purified from an AD brain. Here, we report that GAβ has a conformation distinct from that of soluble Aβ and initiates Aβ aggregation by acting as a seed. Furthermore, GAβ generation in the brain was validated by both immunohistochemical and immunoprecipitation studies. These results imply a mechanism underlying the onset of AD and suggest that an endogenous seed can be a target of therapeutic strategy.Keywords
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