GM1 ganglioside and the seeding of amyloid in Alzheimer's disease: Endogenous seed for alzheimer amyloid

A fundamental question about the pathogenesis of Alzheimer's disease (AD) is how monomeric, nontoxic amyloid beta-protein (A beta) is converted to its toxic aggregates in the brain. The author previously identified a unique A beta species in the AD brain, which is characterized by its binding to GM1 ganglioside (GM1). On the basis of the molecular characteristics of GM1-bound A beta (GA beta), the author hypothesized that GM1 plays a critical role in the process. The author recently examined this possibility using a novel monoclonal antibody raised against purified GA beta and validated that GA beta is endogenously generated in the brain and accelerates A beta assembly by acting as a seed. Furthermore, the author provided a possibility that aging and the expression of apolipoprotein E4 facilitate A beta assembly in the brain through an increase in the GM1 content in the neuronal membranes, which likely induces GA beta generation. The author's results imply a mechanism underlying the onset of AD and also provide a new insight into development of novel therapeutic strategy.