Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain

Yasuo Harigaya, Takaomi C. Saido, Christopher B. Eckman, Cristian Mihail Prada, Mikio Shoji, Steven G Younkin

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

The amyloid β protein (Aβ) deposited in the Alzheimer's disease (AD) brain is heterogeneous at both its amino and carboxyl termini. Recent studies of the genetic forms of AD indicate that the aggregation and deposition of Aβ42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the Aβ species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (Aβ3(pE)). Immunocyto-chemical analysis of AD brains with an antibody specific for Aβ3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of Aβ3(pE)-40 and Aβ3(pE)-42(43) in AD brain compared with other fores. This analysis showed that Aβ3(pE)-40 is closely correlated with the extent of Aβ deposition in blood vessels, whereas Aβ3(pE)-42(43) is not. In addition, Aβ3(pE)-42(43) is an important component of the Aβ deposited in senile plaques of the AD brain, constituting approximately 25% of the total Aβ42(43). In vitro comparison of Aβ1-42 and Aβ3(pE)-42 showed that Aβ3(pE)-42 is highly prone to oligomerization. These findings suggest that Aβ3(pE)-42 may be particularly important in AD pathogenesis. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)422-427
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume276
Issue number2
DOIs
StatePublished - Sep 24 2000

Fingerprint

Pyrrolidonecarboxylic Acid
Amyloidogenic Proteins
Amyloid Plaques
Amyloid
Brain
Alzheimer Disease
Deposits
Blood vessels
Blood Vessels
Serum Amyloid A Protein
Oligomerization
Agglomeration
Enzyme-Linked Immunosorbent Assay
Antibodies

Keywords

  • Alzheimer's disease
  • Amyloid β protein
  • Enzyme-linked immunosorbent assay
  • Pyroglutamate
  • Senile plaques

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain. / Harigaya, Yasuo; Saido, Takaomi C.; Eckman, Christopher B.; Prada, Cristian Mihail; Shoji, Mikio; Younkin, Steven G.

In: Biochemical and Biophysical Research Communications, Vol. 276, No. 2, 24.09.2000, p. 422-427.

Research output: Contribution to journalArticle

Harigaya, Yasuo ; Saido, Takaomi C. ; Eckman, Christopher B. ; Prada, Cristian Mihail ; Shoji, Mikio ; Younkin, Steven G. / Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 276, No. 2. pp. 422-427.
@article{30192e9ace7c4484a1c4873d15657e6c,
title = "Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain",
abstract = "The amyloid β protein (Aβ) deposited in the Alzheimer's disease (AD) brain is heterogeneous at both its amino and carboxyl termini. Recent studies of the genetic forms of AD indicate that the aggregation and deposition of Aβ42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the Aβ species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (Aβ3(pE)). Immunocyto-chemical analysis of AD brains with an antibody specific for Aβ3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of Aβ3(pE)-40 and Aβ3(pE)-42(43) in AD brain compared with other fores. This analysis showed that Aβ3(pE)-40 is closely correlated with the extent of Aβ deposition in blood vessels, whereas Aβ3(pE)-42(43) is not. In addition, Aβ3(pE)-42(43) is an important component of the Aβ deposited in senile plaques of the AD brain, constituting approximately 25{\%} of the total Aβ42(43). In vitro comparison of Aβ1-42 and Aβ3(pE)-42 showed that Aβ3(pE)-42 is highly prone to oligomerization. These findings suggest that Aβ3(pE)-42 may be particularly important in AD pathogenesis. (C) 2000 Academic Press.",
keywords = "Alzheimer's disease, Amyloid β protein, Enzyme-linked immunosorbent assay, Pyroglutamate, Senile plaques",
author = "Yasuo Harigaya and Saido, {Takaomi C.} and Eckman, {Christopher B.} and Prada, {Cristian Mihail} and Mikio Shoji and Younkin, {Steven G}",
year = "2000",
month = "9",
day = "24",
doi = "10.1006/bbrc.2000.3490",
language = "English (US)",
volume = "276",
pages = "422--427",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain

AU - Harigaya, Yasuo

AU - Saido, Takaomi C.

AU - Eckman, Christopher B.

AU - Prada, Cristian Mihail

AU - Shoji, Mikio

AU - Younkin, Steven G

PY - 2000/9/24

Y1 - 2000/9/24

N2 - The amyloid β protein (Aβ) deposited in the Alzheimer's disease (AD) brain is heterogeneous at both its amino and carboxyl termini. Recent studies of the genetic forms of AD indicate that the aggregation and deposition of Aβ42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the Aβ species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (Aβ3(pE)). Immunocyto-chemical analysis of AD brains with an antibody specific for Aβ3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of Aβ3(pE)-40 and Aβ3(pE)-42(43) in AD brain compared with other fores. This analysis showed that Aβ3(pE)-40 is closely correlated with the extent of Aβ deposition in blood vessels, whereas Aβ3(pE)-42(43) is not. In addition, Aβ3(pE)-42(43) is an important component of the Aβ deposited in senile plaques of the AD brain, constituting approximately 25% of the total Aβ42(43). In vitro comparison of Aβ1-42 and Aβ3(pE)-42 showed that Aβ3(pE)-42 is highly prone to oligomerization. These findings suggest that Aβ3(pE)-42 may be particularly important in AD pathogenesis. (C) 2000 Academic Press.

AB - The amyloid β protein (Aβ) deposited in the Alzheimer's disease (AD) brain is heterogeneous at both its amino and carboxyl termini. Recent studies of the genetic forms of AD indicate that the aggregation and deposition of Aβ42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the Aβ species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (Aβ3(pE)). Immunocyto-chemical analysis of AD brains with an antibody specific for Aβ3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of Aβ3(pE)-40 and Aβ3(pE)-42(43) in AD brain compared with other fores. This analysis showed that Aβ3(pE)-40 is closely correlated with the extent of Aβ deposition in blood vessels, whereas Aβ3(pE)-42(43) is not. In addition, Aβ3(pE)-42(43) is an important component of the Aβ deposited in senile plaques of the AD brain, constituting approximately 25% of the total Aβ42(43). In vitro comparison of Aβ1-42 and Aβ3(pE)-42 showed that Aβ3(pE)-42 is highly prone to oligomerization. These findings suggest that Aβ3(pE)-42 may be particularly important in AD pathogenesis. (C) 2000 Academic Press.

KW - Alzheimer's disease

KW - Amyloid β protein

KW - Enzyme-linked immunosorbent assay

KW - Pyroglutamate

KW - Senile plaques

UR - http://www.scopus.com/inward/record.url?scp=0034710784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034710784&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3490

DO - 10.1006/bbrc.2000.3490

M3 - Article

C2 - 11027491

AN - SCOPUS:0034710784

VL - 276

SP - 422

EP - 427

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -