Microglia metabolizes β-amyloid 42 protein and produces a truncated neurotoxic fragment

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Sonia Mazzitelli1,2, Marco Rasile1,2, Ashley S Phillips5, Matteo Tamborini1,2, Fabia Filipello1, Andrew J Doig5, Perdita E Barran5, Erich E Wanker3, Davide Pozzi1 and Michela Matteoli1,4

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Microglia display a dual role in Alzheimerâ??s disease (AD). At early stages of the pathology, microglia is beneficialby phagocytosing amyloid-β42 (Aβ42) and, at later stages, become detrimental, if the inflammatory response is not downregulated. We provide evidence that microglia promotes the formation of a metabolized, toxic form of Aβ42 lacking its C-terminal region, as a result of the enzymatic activity of MMP-9. This N-terminal, truncated Aβ form is highly neurotoxic and more efficient than Aβ42 in inducing endogenous Aβproduction. Furthermore, it is able to promote aggregate formation in the brain of injected wild type mice, where Aβ42 has no effect. By the identification of this novel N-terminal, truncated Aβ form able to initiate amyloid aggregation in vivo even in the absence of mutations known to be associated with AD, our data provide the first evidence for the contribution of microglia to the development of the sporadic form of AD.