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@ARTICLE{Mazzitelli:138852,
author = {Mazzitelli, Sonia and Filipello, Fabia and Rasile, Marco
and Lauranzano, Eliana and Starvaggi-Cucuzza, Chiara and
Tamborini, Matteo and Pozzi, Davide and Barajon, Isabella
and Giorgino, Toni and Natalello, Antonino and Matteoli,
Michela},
title = {{A}myloid-β 1-24 {C}-terminal truncated fragment promotes
amyloid-β 1-42 aggregate formation in the healthy brain.},
journal = {Acta Neuropathologica Communications},
volume = {4},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2020-05174},
pages = {110},
year = {2016},
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.},
keywords = {Alzheimer Disease: metabolism / Alzheimer Disease:
pathology / Amyloid beta-Peptides: administration $\&$
dosage / Amyloid beta-Peptides: metabolism / Animals /
Brain: metabolism / Brain: pathology / Disease Models,
Animal / Humans / Learning Disabilities: metabolism /
Learning Disabilities: pathology / Matrix Metalloproteinase
9: genetics / Matrix Metalloproteinase 9: metabolism /
Memory Disorders: metabolism / Memory Disorders: pathology /
Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice,
Knockout / Mice, Transgenic / Microglia: metabolism /
Microglia: pathology / Motor Activity: physiology / Peptide
Fragments: administration $\&$ dosage / Peptide Fragments:
metabolism / Plaque, Amyloid: metabolism / Plaque, Amyloid:
pathology / Protein Folding / Protein Multimerization /
Social Behavior / Amyloid beta-Peptides (NLM Chemicals) /
Peptide Fragments (NLM Chemicals) / amyloid beta-peptide
(1-24) (NLM Chemicals) / amyloid beta-protein (1-42) (NLM
Chemicals) / Matrix Metalloproteinase 9 (NLM Chemicals) /
Mmp9 protein, mouse (NLM Chemicals)},
cin = {AG Heutink},
ddc = {610},
cid = {I:(DE-2719)1210002},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27724899},
pmc = {pmc:PMC5057504},
doi = {10.1186/s40478-016-0381-9},
url = {https://pub.dzne.de/record/138852},
}