Dataset Information

Aggregation States of A?1-40, A?1-42 and A?p3-42 Amyloid Beta Peptides: A SANS Study.

ABSTRACT: Aggregation states of amyloid beta peptides for amyloid beta A ? 1 - 40 to A ? 1 - 42 and A ? p 3 - 42 are investigated through small angle neutron scattering (SANS). The knowledge of these small peptides and their aggregation state are of key importance for the comprehension of neurodegenerative diseases (e.g., Alzheimer's disease). The SANS technique allows to study the size and fractal nature of the monomers, oligomers and fibrils of the three different peptides. Results show that all the investigated peptides have monomers with a radius of gyration of the order of 10 Å, while the oligomers and fibrils display differences in size and aggregation ability, with A ? p 3 - 42 showing larger oligomers. These properties are strictly related to the toxicity of the corresponding amyloid peptide and indeed to the development of the associated disease.

SUBMITTER: Festa G

PROVIDER: S-EPMC6747079 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Aggregation States of Aβ1-40, Aβ1-42 and Aβp3-42 Amyloid Beta Peptides: A SANS Study.

Festa Giulia G Mallamace Francesco F Sancesario Giulia Maria GM Corsaro Carmelo C Mallamace Domenico D Fazio Enza E Arcidiacono Laura L Garcia Sakai Victoria V Senesi Roberto R Preziosi Enrico E Sancesario Giuseppe G Andreani Carla C

International journal of molecular sciences 20190824 17

Aggregation states of amyloid beta peptides for amyloid beta A β 1 - 40 to A β 1 - 42 and A β p 3 - 42 are investigated through small angle neutron scattering (SANS). The knowledge of these small peptides and their aggregation state are of key importance for the comprehension of neurodegenerative diseases (e.g., Alzheimer's disease). The SANS technique allows to study the size and fractal nature of the monomers, oligomers and fibrils of the three different peptides. Results show that all the inv ...[more]

PMID: 31450543

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Project description:Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET-/plasma-, PET-/plasma+, PET+/plasma-, PET+/plasma+) using Alzheimer's Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET-/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET-/plasma+ showed intermediate changes between PET-/plasma- and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma- represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

Dataset Information

Aggregation States of A?1-40, A?1-42 and A?p3-42 Amyloid Beta Peptides: A SANS Study.

Publications

Aggregation States of A<i>β</i><sub>1-40</sub>, A<i>β</i><sub>1-42</sub> and A<i>β</i>p<sub>3-42</sub> Amyloid Beta Peptides: A SANS Study.

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