TY  - JOUR
AU  - Mazzitelli, Sonia
AU  - Filipello, Fabia
AU  - Rasile, Marco
AU  - Lauranzano, Eliana
AU  - Starvaggi-Cucuzza, Chiara
AU  - Tamborini, Matteo
AU  - Pozzi, Davide
AU  - Barajon, Isabella
AU  - Giorgino, Toni
AU  - Natalello, Antonino
AU  - Matteoli, Michela
TI  - Amyloid-β 1-24 C-terminal truncated fragment promotes amyloid-β 1-42 aggregate formation in the healthy brain.
JO  - Acta Neuropathologica Communications
VL  - 4
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DZNE-2020-05174
SP  - 110
PY  - 2016
AB  - 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.
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Amyloid beta-Peptides: administration & dosage
KW  - Amyloid beta-Peptides: metabolism
KW  - Animals
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Disease Models, Animal
KW  - Humans
KW  - Learning Disabilities: metabolism
KW  - Learning Disabilities: pathology
KW  - Matrix Metalloproteinase 9: genetics
KW  - Matrix Metalloproteinase 9: metabolism
KW  - Memory Disorders: metabolism
KW  - Memory Disorders: pathology
KW  - Mice
KW  - Mice, Inbred BALB C
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Mice, Transgenic
KW  - Microglia: metabolism
KW  - Microglia: pathology
KW  - Motor Activity: physiology
KW  - Peptide Fragments: administration & dosage
KW  - Peptide Fragments: metabolism
KW  - Plaque, Amyloid: metabolism
KW  - Plaque, Amyloid: pathology
KW  - Protein Folding
KW  - Protein Multimerization
KW  - Social Behavior
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - amyloid beta-peptide (1-24) (NLM Chemicals)
KW  - amyloid beta-protein (1-42) (NLM Chemicals)
KW  - Matrix Metalloproteinase 9 (NLM Chemicals)
KW  - Mmp9 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27724899
C2  - pmc:PMC5057504
DO  - DOI:10.1186/s40478-016-0381-9
UR  - https://pub.dzne.de/record/138852
ER  -