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
N1 - Publisher Copyright:
© 2015 American Chemical Society.
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
U2 - 10.1021/acschemneuro.5b00231
DO - 10.1021/acschemneuro.5b00231
M3 - Article
C2 - 26448453
AN - SCOPUS:84950288771
SN - 1948-7193
VL - 6
SP - 1981
EP - 1989
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 12
ER -