One of the binding proteins for administered amyloid-β appears to be anti-Aβ IgG antibody in amyloid plaques
Takahashi, Reisuke H ; Yokotsuka, Mayumi ; Nakamura, Ayako ; Nagao, Toshitaka ; Gouras, Gunnar K LU
and Uchihara, Toshiki
(2025)
In Journal of Alzheimer's disease : JAD
p.1-12
- Abstract
BackgroundAmyloid-β peptides (Aβ) applied to Alzheimer's disease (AD) brain bind to amyloid plaques (APs) and this binding is saturable. Meanwhile, anti-immunoglobulin G (IgG) antibodies label APs. Considering the saturable binding of Aβ to APs and the localization of IgGs in APs, specific binding proteins (BPs) for the applied Aβ could be anti-Aβ IgG antibodies (anti-AβAbs) in APs.ObjectiveOur objective is to demonstrate whether anti-AβAbs are the BPs for administered Aβ in APs.MethodsTo identify the binding specificity, we established a tissue competition assay utilizing the competitiveness of ligand specificity to BPs. Biotinylated Aβ
42 (Bio42) was applied as ligand to AD brain sections. Second, Bio42 and IgG (anti-AβAbs) in... (More)BackgroundAmyloid-β peptides (Aβ) applied to Alzheimer's disease (AD) brain bind to amyloid plaques (APs) and this binding is saturable. Meanwhile, anti-immunoglobulin G (IgG) antibodies label APs. Considering the saturable binding of Aβ to APs and the localization of IgGs in APs, specific binding proteins (BPs) for the applied Aβ could be anti-Aβ IgG antibodies (anti-AβAbs) in APs.ObjectiveOur objective is to demonstrate whether anti-AβAbs are the BPs for administered Aβ in APs.MethodsTo identify the binding specificity, we established a tissue competition assay utilizing the competitiveness of ligand specificity to BPs. Biotinylated Aβ
(Less)
42 (Bio42) was applied as ligand to AD brain sections. Second, Bio42 and IgG (anti-AβAbs) in APs were observed by double immunofluorescent labeling with ultrahigh-resolution imaging. Finally, to demonstrate the direct binding of Bio42 to anti-AβAbs we employed immunoprecipitation-western blotting.ResultsWith the tissue competition assay, binding of Bio42 to APs was competitively blocked by coincubation with competitive Aβ
42 (Pep42) in a dose-dependent manner but not with non-competitive Aβ
40 (Pep40). Colocalization of Bio42 and anti-AβAbs was clearly detected with ultrahigh-resolution imaging. Anti-AβAbs were immunoprecipitated by Bio42 and immunoblotted by anti-IgG antibodies.ConclusionsWe have provided evidence that the applied Aβ specifically binds to anti-AβAbs rather than aggregating with Aβ in APs. Our results support the scenario that anti-AβAbs surround and/or sequester Aβ from biological fluids to APs, thereby affecting the amount of Aβ in body fluids. It might be important to consider anti-AβAbs in APs for more effective diagnosis and therapy for AD.
- author
- Takahashi, Reisuke H
; Yokotsuka, Mayumi
; Nakamura, Ayako
; Nagao, Toshitaka
; Gouras, Gunnar K
LU
and Uchihara, Toshiki
- organization
- publishing date
- 2025-10-30
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Journal of Alzheimer's disease : JAD
- pages
- 1 - 12
- publisher
- SAGE Publications
- external identifiers
-
- pmid:41166188
- ISSN
- 1387-2877
- DOI
- 10.1177/13872877251389631
- language
- English
- LU publication?
- yes
- id
- 84fa2d77-e5ce-4661-b0d9-dd017836f46b
- date added to LUP
- 2025-11-12 13:30:37
- date last changed
- 2025-11-12 14:24:43
@article{84fa2d77-e5ce-4661-b0d9-dd017836f46b,
abstract = {{<p>BackgroundAmyloid-β peptides (Aβ) applied to Alzheimer's disease (AD) brain bind to amyloid plaques (APs) and this binding is saturable. Meanwhile, anti-immunoglobulin G (IgG) antibodies label APs. Considering the saturable binding of Aβ to APs and the localization of IgGs in APs, specific binding proteins (BPs) for the applied Aβ could be anti-Aβ IgG antibodies (anti-AβAbs) in APs.ObjectiveOur objective is to demonstrate whether anti-AβAbs are the BPs for administered Aβ in APs.MethodsTo identify the binding specificity, we established a tissue competition assay utilizing the competitiveness of ligand specificity to BPs. Biotinylated Aβ<br>
42 (Bio42) was applied as ligand to AD brain sections. Second, Bio42 and IgG (anti-AβAbs) in APs were observed by double immunofluorescent labeling with ultrahigh-resolution imaging. Finally, to demonstrate the direct binding of Bio42 to anti-AβAbs we employed immunoprecipitation-western blotting.ResultsWith the tissue competition assay, binding of Bio42 to APs was competitively blocked by coincubation with competitive Aβ <br>
42 (Pep42) in a dose-dependent manner but not with non-competitive Aβ<br>
40 (Pep40). Colocalization of Bio42 and anti-AβAbs was clearly detected with ultrahigh-resolution imaging. Anti-AβAbs were immunoprecipitated by Bio42 and immunoblotted by anti-IgG antibodies.ConclusionsWe have provided evidence that the applied Aβ specifically binds to anti-AβAbs rather than aggregating with Aβ in APs. Our results support the scenario that anti-AβAbs surround and/or sequester Aβ from biological fluids to APs, thereby affecting the amount of Aβ in body fluids. It might be important to consider anti-AβAbs in APs for more effective diagnosis and therapy for AD.<br>
</p>}},
author = {{Takahashi, Reisuke H and Yokotsuka, Mayumi and Nakamura, Ayako and Nagao, Toshitaka and Gouras, Gunnar K and Uchihara, Toshiki}},
issn = {{1387-2877}},
language = {{eng}},
month = {{10}},
pages = {{1--12}},
publisher = {{SAGE Publications}},
series = {{Journal of Alzheimer's disease : JAD}},
title = {{One of the binding proteins for administered amyloid-β appears to be anti-Aβ IgG antibody in amyloid plaques}},
url = {{http://dx.doi.org/10.1177/13872877251389631}},
doi = {{10.1177/13872877251389631}},
year = {{2025}},
}