Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease

Riddhi U. Bodani, Urmi Sengupta, Diana L. Castillo-Carranza, Marcos J. Guerrero-Muñoz, Julia E. Gerson, Jai Rudra, Rakez Kayed

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.

Original languageEnglish (US)
Pages (from-to)1981-1989
Number of pages9
JournalACS Chemical Neuroscience
Volume6
Issue number12
DOIs
StatePublished - Dec 16 2015

Fingerprint

Poisons
Oligomers
Amyloid
Alzheimer Disease
Peptides
Antibodies
Antibody Specificity
Amyloid Plaques
Neurodegenerative diseases
Neurodegenerative Diseases
Immunotherapy
Epitopes
Protein Isoforms
Pathology
Amino Acids
Brain
Agglomeration

Keywords

  • Amyloid oligomers
  • repeated sequence
  • small peptide

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

Bodani, R. U., Sengupta, U., Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Gerson, J. E., Rudra, J., & Kayed, R. (2015). Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease. ACS Chemical Neuroscience, 6(12), 1981-1989. https://doi.org/10.1021/acschemneuro.5b00231

Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease. / Bodani, Riddhi U.; Sengupta, Urmi; Castillo-Carranza, Diana L.; Guerrero-Muñoz, Marcos J.; Gerson, Julia E.; Rudra, Jai; Kayed, Rakez.

In: ACS Chemical Neuroscience, Vol. 6, No. 12, 16.12.2015, p. 1981-1989.

Research output: Contribution to journalArticle

Bodani, RU, Sengupta, U, Castillo-Carranza, DL, Guerrero-Muñoz, MJ, Gerson, JE, Rudra, J & Kayed, R 2015, 'Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease', ACS Chemical Neuroscience, vol. 6, no. 12, pp. 1981-1989. https://doi.org/10.1021/acschemneuro.5b00231
Bodani RU, Sengupta U, Castillo-Carranza DL, Guerrero-Muñoz MJ, Gerson JE, Rudra J et al. Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease. ACS Chemical Neuroscience. 2015 Dec 16;6(12):1981-1989. https://doi.org/10.1021/acschemneuro.5b00231
Bodani, Riddhi U. ; Sengupta, Urmi ; Castillo-Carranza, Diana L. ; Guerrero-Muñoz, Marcos J. ; Gerson, Julia E. ; Rudra, Jai ; Kayed, Rakez. / Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease. In: ACS Chemical Neuroscience. 2015 ; Vol. 6, No. 12. pp. 1981-1989.
@article{8a14fa0e5e0942a8903e12a195fa4075,
title = "Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease",
abstract = "Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.",
keywords = "Amyloid oligomers, repeated sequence, small peptide",
author = "Bodani, {Riddhi U.} and Urmi Sengupta and Castillo-Carranza, {Diana L.} and Guerrero-Mu{\~n}oz, {Marcos J.} and Gerson, {Julia E.} and Jai Rudra and Rakez Kayed",
year = "2015",
month = "12",
day = "16",
doi = "10.1021/acschemneuro.5b00231",
language = "English (US)",
volume = "6",
pages = "1981--1989",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease

AU - Bodani, Riddhi U.

AU - Sengupta, Urmi

AU - Castillo-Carranza, Diana L.

AU - Guerrero-Muñoz, Marcos J.

AU - Gerson, Julia E.

AU - Rudra, Jai

AU - Kayed, Rakez

PY - 2015/12/16

Y1 - 2015/12/16

N2 - Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.

AB - Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.

KW - Amyloid oligomers

KW - repeated sequence

KW - small peptide

UR - http://www.scopus.com/inward/record.url?scp=84950288771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950288771&partnerID=8YFLogxK

U2 - 10.1021/acschemneuro.5b00231

DO - 10.1021/acschemneuro.5b00231

M3 - Article

VL - 6

SP - 1981

EP - 1989

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 12

ER -