Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease

Omar Ali El-Agnaf, Devinder S. Mahil, Bhroma P. Patel, Brian M. Austen

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

β-Amyloid protein (Aβ) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Aβ peptides which gives high yield and purity of the initial crude preparation.

Original languageEnglish
Pages (from-to)1003-1007
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume273
Issue number3
DOIs
Publication statusPublished - 14 Jul 2000
Externally publishedYes

Fingerprint

Oligomerization
Amyloid
Toxicity
Alzheimer Disease
Oligomers
Serum Amyloid A Protein
Solid-Phase Synthesis Techniques
Poisons
Amyloid Plaques
Neuroblastoma
Brain
Enzyme-Linked Immunosorbent Assay
Association reactions
Peptides

Keywords

  • Aggregation
  • Alzheimer's disease
  • Amyloid
  • Oligomerization
  • Solid-phase peptide synthesis
  • Toxicity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease. / Ali El-Agnaf, Omar; Mahil, Devinder S.; Patel, Bhroma P.; Austen, Brian M.

In: Biochemical and Biophysical Research Communications, Vol. 273, No. 3, 14.07.2000, p. 1003-1007.

Research output: Contribution to journalArticle

Ali El-Agnaf, Omar ; Mahil, Devinder S. ; Patel, Bhroma P. ; Austen, Brian M. / Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 273, No. 3. pp. 1003-1007.
@article{74354d3084e44757a0e635085274659b,
title = "Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease",
abstract = "β-Amyloid protein (Aβ) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Aβ peptides which gives high yield and purity of the initial crude preparation.",
keywords = "Aggregation, Alzheimer's disease, Amyloid, Oligomerization, Solid-phase peptide synthesis, Toxicity",
author = "{Ali El-Agnaf}, Omar and Mahil, {Devinder S.} and Patel, {Bhroma P.} and Austen, {Brian M.}",
year = "2000",
month = "7",
day = "14",
doi = "10.1006/bbrc.2000.3051",
language = "English",
volume = "273",
pages = "1003--1007",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease

AU - Ali El-Agnaf, Omar

AU - Mahil, Devinder S.

AU - Patel, Bhroma P.

AU - Austen, Brian M.

PY - 2000/7/14

Y1 - 2000/7/14

N2 - β-Amyloid protein (Aβ) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Aβ peptides which gives high yield and purity of the initial crude preparation.

AB - β-Amyloid protein (Aβ) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Aβ peptides which gives high yield and purity of the initial crude preparation.

KW - Aggregation

KW - Alzheimer's disease

KW - Amyloid

KW - Oligomerization

KW - Solid-phase peptide synthesis

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=0034647786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034647786&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3051

DO - 10.1006/bbrc.2000.3051

M3 - Article

C2 - 10891362

AN - SCOPUS:0034647786

VL - 273

SP - 1003

EP - 1007

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -