scholarly journals Assessment of the Bioactivity of Antibodies against β-Amyloid Peptide in vitro and in vivo

2004 ◽  
Vol 1 (4-5) ◽  
pp. 160-167 ◽  
Author(s):  
M. Hasan Mohajeri ◽  
Meret N.M. Gaugler ◽  
Julia Martinez ◽  
Jay Tracy ◽  
Hong Li ◽  
...  
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Mechanism of Cellular Formation and In Vivo Seeding Effects of Hexameric β-amyloid Assemblies

2021 ◽  
Author(s):  
Céline Vrancx ◽  
Devkee M Vadukul ◽  
Nuria Suelves ◽  
Sabrina Contino ◽  
Ludovic D'Auria ◽  
...  
Keyword(s):  
Senile Plaques ◽  
Amyloid Peptide ◽  
Secretase Activity ◽  
Aβ Aggregation ◽  
Cellular Context ◽  
Β Amyloid ◽  
Β Amyloid Peptide ◽  
Aβ Generation

Abstract The β-amyloid peptide (Aβ) is the main constituent of senile plaques, a typical hallmark of Alzheimer’s disease (AD). Monomeric Aβ is generated through sequential processing of the amyloid precursor protein (APP), with a final step involving γ-secretase activity. In AD, Aβ monomers assemble in oligomers and ultimately fibrils depositing in plaques. Importantly, Aβ toxicity appears related to its soluble oligomeric intermediates. In particular, recombinant Aβ studies described Aβ hexamers as critical oligomeric nuclei. We recently identified hexameric Aβ assemblies in a cellular model, and revealed their ability to enhance recombinant Aβ aggregation in vitro. Here, we assessed the contribution of similar hexameric-like Aβ assemblies to the development of amyloid pathology. We report their early presence in both transgenic mice brains exhibiting human Aβ pathology and cerebrospinal fluid of AD patients, suggesting hexameric Aβ as a putative novel AD biomarker. Using isolated cell-derived hexameric Aβ, we report the potential of these assemblies to seed other human Aβ species, resulting in neuronal toxicity in vitro and amyloid deposition aggravation in vivo. In order to identify key contributors to their formation in a cellular context, we investigated the role of presenilin-1 (PS1) and presenilin-2 (PS2) in the formation of hexameric-like Aβ assemblies. As catalytic subunits of the γ-secretase complex, PS1 and PS2 can differentially participate in Aβ generation. Using CRISPR-Cas9-modified neuronal-like cell lines knockdown for each of the two presenilins, we present experimental evidence suggesting a direct link between the PS2-dependent pathway and the release of hexameric-like Aβ assemblies in extracellular vesicles.

A spiropyran-based fluorescent probe for the specific detection of β-amyloid peptide oligomers in Alzheimer's disease

2016 ◽  
Vol 52 (57) ◽  
pp. 8865-8868 ◽  
Author(s):  
Guanglei Lv ◽  
Anyang Sun ◽  
Peng Wei ◽  
Ning Zhang ◽  
Haichuang Lan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fluorescent Probe ◽  
Amyloid Peptide ◽  
Specific Detection ◽  
Aβ Oligomers ◽  
Β Amyloid ◽  
Β Amyloid Peptide

A fluorescent probe for the specific detection of Aβ oligomers in Alzheimer's disease both in vitro and in vivo was developed.

In vitro aggregation facilitates β-amyloid peptide-(25–35)-induced amnesia in the rat

1997 ◽  
Vol 319 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Stéphanie Delobette ◽  
Alain Privat ◽  
Tangui Maurice
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Modulation of β-amyloid aggregation by graphene quantum dots

2019 ◽  
Vol 6 (6) ◽  
pp. 190271 ◽  
Author(s):  
Changliang Liu ◽  
Huan Huang ◽  
Lilusi Ma ◽  
Xiaocui Fang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Structural Changes ◽  
Graphene Quantum Dots ◽  
Amyloid Peptide ◽  
Therapeutic Drug ◽  
Amyloid Aggregation ◽  
Β Amyloid ◽  
Regulatory Effects ◽  
Β Amyloid Peptide

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1–42 β-amyloid (Aβ 1–42 ) aggregation. GQDs displayed significant regulatory effects on the aggregation of Aβ 1–42 peptide as detected by thioflavin T (ThT) assay. Then, the changes of confirmations and structures induced by GQDs on the Aβ 1–42 aggregation were monitored by circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscope (TEM). The in vitro cytotoxicity experiments further demonstrated the feasibility of GQDs on the regulation of Aβ 1–42 aggregation. Meanwhile, the structural changes of a Aβ 1–42 /GQDs mixture in different pH revealed that electrostatic interaction was the major driving force in the co-assembly process of Aβ 1–42 and GQDs. The proposed mechanism of the regulatory effects of GQDs on the Aβ 1–42 aggregation was also deduced reasonably. This work not only demonstrated the potential feasibility of GQDs as therapeutic drug for AD but also clarified the regulatory mechanism of GQDs on the Aβ 1–42 aggregation.

In Vivo Aggregation of β-Amyloid Peptide Variants

2002 ◽  
Vol 71 (4) ◽  
pp. 1616-1625 ◽  
Author(s):  
David S. Fay ◽  
Amy Fluet ◽  
Carolyn J. Johnson ◽  
Christopher D. Link
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase

2003 ◽  
Vol 13 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Joanna L. Jankowsky ◽  
Daniel J. Fadale ◽  
Jeffrey Anderson ◽  
Guilian M. Xu ◽  
Victoria Gonzales ◽  
...  
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Mechanism of cellular production and in vivo seeding effects of hexameric β-amyloid assemblies

2020 ◽  
Author(s):  
Céline Vrancx ◽  
Devkee M Vadukul ◽  
Sabrina Contino ◽  
Nuria Suelves ◽  
Ludovic D’Auria ◽  
...  
Keyword(s):  
Cell Lines ◽  
Amyloid Deposition ◽  
Amyloid Peptide ◽  
Intracerebral Injection ◽  
Cytotoxic Effects ◽  
Wide Range ◽  
Β Amyloid ◽  
5Xfad Mice

AbstractBackgroundThe β-amyloid peptide (Aβ) plays a key role in Alzheimer’s disease. After its production by catabolism of the amyloid precursor protein (APP) through the action of presenilin 1 (PS1)- or presenilin 2 (PS2)-dependent γ-secretases, monomeric Aβ can assemble in oligomers. In a pathological context, this eventually leads to the formation of fibrils, which deposit in senile plaques. Many studies suggest that Aβ toxicity is related to its soluble oligomeric intermediates. Among these, our interest focuses on hexameric Aβ, which acts as a nucleus for Aβ self-assembly.MethodsBiochemical analyses were used to identify hexameric Aβ in a wide range of models; cell lines, cerebrospinal fluid from cognitively impaired patients and transgenic mice exhibiting human Aβ pathology (5xFAD). We isolated this assembly and assessed both its effect on primary neuron viability in vitro, and its contribution to amyloid deposition in vivo following intracerebral injection. In both cases, we used wild-type mice (C57BL/6) to mimic an environment where hexameric Aβ is present alone and 5xFAD mice to incubate hexameric Aβ in a context where human Aβ species are pre-existing. Using CRISPR-Cas9, we produced stable knockdown human cell lines for either PS1 or PS2 to elucidate their contribution to the formation of hexameric Aβ.ResultsIn WT mice, we found that neither in vitro or in vivo exposure to hexameric Aβ was sufficient to induce cytotoxic effects or amyloid deposition. In 5xFAD mice, we observed a significant increase in neuronal death in vitro following exposure to 5μM hexameric Aβ, as well as a 1.47-fold aggravation of amyloid deposition in vivo. At the cellular level, we found hexameric Aβ in extracellular vesicles and observed a strong decrease in its excretion when PS2 was knocked down by 60%.ConclusionsOur results indicate the absence of cytotoxic effects of cell-derived hexameric Aβ by itself, but its capacity to aggravate amyloid deposition by seeding other Aβ species. We propose an important role for PS2 in the formation of this particular assembly in vesicular entities, in line with previous reports linking the restricted location of PS2 in acidic compartments to the production of more aggregation-prone Aβ.

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