Title |
Amyloid-β 1–24 C-terminal truncated fragment promotes amyloid-β 1–42 aggregate formation in the healthy brain
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Published in |
Acta Neuropathologica Communications, October 2016
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DOI | 10.1186/s40478-016-0381-9 |
Pubmed ID | |
Authors |
Sonia Mazzitelli, Fabia Filipello, Marco Rasile, Eliana Lauranzano, Chiara Starvaggi-Cucuzza, Matteo Tamborini, Davide Pozzi, Isabella Barajon, Toni Giorgino, Antonino Natalello, Michela Matteoli |
Abstract |
Substantial data indicate that amyloid-β (Aβ), the major component of senile plaques, plays a central role in Alzheimer's Disease and indeed the assembly of naturally occurring amyloid peptides into cytotoxic aggregates is linked to the disease pathogenesis. Although Aβ42 is a highly aggregating form of Aβ, the co-occurrence of shorter Aβ peptides might affect the aggregation potential of the Aβ pool. In this study we aimed to assess whether the structural behavior of human Aβ42 peptide inside the brain is influenced by the concomitant presence of N-terminal fragments produced by the proteolytic activity of glial cells. We show that the occurrence of the human C-terminal truncated 1-24 Aβ fragment impairs Aβ42 clearance through blood brain barrier and promotes the formation of Aβ42 aggregates even in the healthy brain. By showing that Aβ1-24 has seeding properties for aggregate formation in intracranially injected wild type mice, our study provide the proof-of-concept that peptides produced upon Aβ42 cleavage by activated glial cells may cause phenotypic defects even in the absence of genetic mutations associated with Alzheimer's Disease, possibly contributing to the development of the sporadic form of the pathology. |
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Mendeley readers
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