RAGE-aβ interactions in the pathophysiology of Alzheimer's disease

Shi Du Yan, David Stern, Michael D. Kane, Yu Min Kuo, Heather C. Lampert, Alex E. Roher

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

RAGE is a cell surface molecule primarily identified for its capacity to bind advanced glycation end-products and amphoterin. Immunocytochemical studies demonstrated that in Alzheimer's disease (AD) the expression of RAGE is elevated in neurons close to neuritic plaque beta-amyloid (Aβ) deposits and in the cells of Aβ containing vessels. Cross-linking of surface bound Aβ 1-40 to endothelial cells, yielded a band of 50 kDa identified as RAGE. Using the soluble extracellular domain of recombinant human RAGE, we found that Aβ binds to RAGE with a Kd = 57 ± 14 nM, a value close to those found for mouse brain endothelial cells and rat cortical neurons. The interaction of Aβ with RAGE in neuronal, endothelial, and RAGE-transfected COS-1 cells induced oxidative stress, as assessed by the TBARS and MTT assays. ELISA demonstrated a 2.5 times increase of RAGE in AD over control brains. Activated microglia also showed elevated expression of RAGE. In the BV-2 microglial cell line, RAGE bound Aβ in a dose dependent manner with a Kd of 25 ± 9 nM. Soluble Aβ induced the migration of microglia along a concentration gradient, while immobilized Aβ arrested this migration. Aβ- RAGE interaction also activated NF-κB, resulting in neuronal up-regulation of macrophage-colony stimulating factor (M-CSF) which also induced microglial migration. Taken together, our data suggest that RAGE-Aβ interactions play an important role in the pathophysiology of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalRestorative Neurology and Neuroscience
Volume12
Issue number2-3
StatePublished - Jun 1 1998
Externally publishedYes

Fingerprint

Alzheimer Disease
Amyloid Plaques
Microglia
Endothelial Cells
HMGB1 Protein
Neurons
Advanced Glycosylation End Products
Macrophage Colony-Stimulating Factor
COS Cells
Brain
Oxidative Stress
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Cell Line

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Yan, S. D., Stern, D., Kane, M. D., Kuo, Y. M., Lampert, H. C., & Roher, A. E. (1998). RAGE-aβ interactions in the pathophysiology of Alzheimer's disease. Restorative Neurology and Neuroscience, 12(2-3), 167-173.

RAGE-aβ interactions in the pathophysiology of Alzheimer's disease. / Yan, Shi Du; Stern, David; Kane, Michael D.; Kuo, Yu Min; Lampert, Heather C.; Roher, Alex E.

In: Restorative Neurology and Neuroscience, Vol. 12, No. 2-3, 01.06.1998, p. 167-173.

Research output: Contribution to journalArticle

Yan, SD, Stern, D, Kane, MD, Kuo, YM, Lampert, HC & Roher, AE 1998, 'RAGE-aβ interactions in the pathophysiology of Alzheimer's disease', Restorative Neurology and Neuroscience, vol. 12, no. 2-3, pp. 167-173.
Yan SD, Stern D, Kane MD, Kuo YM, Lampert HC, Roher AE. RAGE-aβ interactions in the pathophysiology of Alzheimer's disease. Restorative Neurology and Neuroscience. 1998 Jun 1;12(2-3):167-173.
Yan, Shi Du ; Stern, David ; Kane, Michael D. ; Kuo, Yu Min ; Lampert, Heather C. ; Roher, Alex E. / RAGE-aβ interactions in the pathophysiology of Alzheimer's disease. In: Restorative Neurology and Neuroscience. 1998 ; Vol. 12, No. 2-3. pp. 167-173.
@article{1491e0a9ccce4052b14f13dba8e086f2,
title = "RAGE-aβ interactions in the pathophysiology of Alzheimer's disease",
abstract = "RAGE is a cell surface molecule primarily identified for its capacity to bind advanced glycation end-products and amphoterin. Immunocytochemical studies demonstrated that in Alzheimer's disease (AD) the expression of RAGE is elevated in neurons close to neuritic plaque beta-amyloid (Aβ) deposits and in the cells of Aβ containing vessels. Cross-linking of surface bound Aβ 1-40 to endothelial cells, yielded a band of 50 kDa identified as RAGE. Using the soluble extracellular domain of recombinant human RAGE, we found that Aβ binds to RAGE with a Kd = 57 ± 14 nM, a value close to those found for mouse brain endothelial cells and rat cortical neurons. The interaction of Aβ with RAGE in neuronal, endothelial, and RAGE-transfected COS-1 cells induced oxidative stress, as assessed by the TBARS and MTT assays. ELISA demonstrated a 2.5 times increase of RAGE in AD over control brains. Activated microglia also showed elevated expression of RAGE. In the BV-2 microglial cell line, RAGE bound Aβ in a dose dependent manner with a Kd of 25 ± 9 nM. Soluble Aβ induced the migration of microglia along a concentration gradient, while immobilized Aβ arrested this migration. Aβ- RAGE interaction also activated NF-κB, resulting in neuronal up-regulation of macrophage-colony stimulating factor (M-CSF) which also induced microglial migration. Taken together, our data suggest that RAGE-Aβ interactions play an important role in the pathophysiology of Alzheimer's disease.",
author = "Yan, {Shi Du} and David Stern and Kane, {Michael D.} and Kuo, {Yu Min} and Lampert, {Heather C.} and Roher, {Alex E.}",
year = "1998",
month = "6",
day = "1",
language = "English (US)",
volume = "12",
pages = "167--173",
journal = "Restorative Neurology and Neuroscience",
issn = "0922-6028",
publisher = "IOS Press",
number = "2-3",

}

TY - JOUR

T1 - RAGE-aβ interactions in the pathophysiology of Alzheimer's disease

AU - Yan, Shi Du

AU - Stern, David

AU - Kane, Michael D.

AU - Kuo, Yu Min

AU - Lampert, Heather C.

AU - Roher, Alex E.

PY - 1998/6/1

Y1 - 1998/6/1

N2 - RAGE is a cell surface molecule primarily identified for its capacity to bind advanced glycation end-products and amphoterin. Immunocytochemical studies demonstrated that in Alzheimer's disease (AD) the expression of RAGE is elevated in neurons close to neuritic plaque beta-amyloid (Aβ) deposits and in the cells of Aβ containing vessels. Cross-linking of surface bound Aβ 1-40 to endothelial cells, yielded a band of 50 kDa identified as RAGE. Using the soluble extracellular domain of recombinant human RAGE, we found that Aβ binds to RAGE with a Kd = 57 ± 14 nM, a value close to those found for mouse brain endothelial cells and rat cortical neurons. The interaction of Aβ with RAGE in neuronal, endothelial, and RAGE-transfected COS-1 cells induced oxidative stress, as assessed by the TBARS and MTT assays. ELISA demonstrated a 2.5 times increase of RAGE in AD over control brains. Activated microglia also showed elevated expression of RAGE. In the BV-2 microglial cell line, RAGE bound Aβ in a dose dependent manner with a Kd of 25 ± 9 nM. Soluble Aβ induced the migration of microglia along a concentration gradient, while immobilized Aβ arrested this migration. Aβ- RAGE interaction also activated NF-κB, resulting in neuronal up-regulation of macrophage-colony stimulating factor (M-CSF) which also induced microglial migration. Taken together, our data suggest that RAGE-Aβ interactions play an important role in the pathophysiology of Alzheimer's disease.

AB - RAGE is a cell surface molecule primarily identified for its capacity to bind advanced glycation end-products and amphoterin. Immunocytochemical studies demonstrated that in Alzheimer's disease (AD) the expression of RAGE is elevated in neurons close to neuritic plaque beta-amyloid (Aβ) deposits and in the cells of Aβ containing vessels. Cross-linking of surface bound Aβ 1-40 to endothelial cells, yielded a band of 50 kDa identified as RAGE. Using the soluble extracellular domain of recombinant human RAGE, we found that Aβ binds to RAGE with a Kd = 57 ± 14 nM, a value close to those found for mouse brain endothelial cells and rat cortical neurons. The interaction of Aβ with RAGE in neuronal, endothelial, and RAGE-transfected COS-1 cells induced oxidative stress, as assessed by the TBARS and MTT assays. ELISA demonstrated a 2.5 times increase of RAGE in AD over control brains. Activated microglia also showed elevated expression of RAGE. In the BV-2 microglial cell line, RAGE bound Aβ in a dose dependent manner with a Kd of 25 ± 9 nM. Soluble Aβ induced the migration of microglia along a concentration gradient, while immobilized Aβ arrested this migration. Aβ- RAGE interaction also activated NF-κB, resulting in neuronal up-regulation of macrophage-colony stimulating factor (M-CSF) which also induced microglial migration. Taken together, our data suggest that RAGE-Aβ interactions play an important role in the pathophysiology of Alzheimer's disease.

UR - http://www.scopus.com/inward/record.url?scp=0031821610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031821610&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 167

EP - 173

JO - Restorative Neurology and Neuroscience

JF - Restorative Neurology and Neuroscience

SN - 0922-6028

IS - 2-3

ER -