Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Free Access

Insights into Caspase-Mediated Apoptotic Pathways Induced by Amyloid-β in Cerebral Microvascular Endothelial Cells

Fossati S.a · Ghiso J.a, b · Rostagno A.a

Author affiliations

Departments of aPathology and bPsychiatry, New York University School of Medicine, New York, N.Y., USA

Corresponding Author

Silvia Fossati, PhD

Department of Pathology, New York University School of Medicine

550 First Avenue (MSB-556)

New York, NY 10016 (USA)

Tel. +1 212 263 7724, E-Mail silvia.fossati@nyumc.org

Related Articles for ""

Neurodegenerative Dis 2012;10:324–328

Do you have an account?

Login Information

Contact Information

By signing up for MyKarger you will automatically participate in our year-End raffle.
If you Then Do Not wish To participate, please uncheck the following box.

Yes, I wish To participate In the year-End raffle And Get the chance To win some Of our most interesting books, And other attractive prizes.

I have read the Karger Terms and Conditions and agree.


Background: The vascular deposition of amyloid known as cerebral amyloid angiopathy (CAA) – an age-associated condition and a common finding in Alzheimer’s disease – compromises cerebral blood flow, causing macro/microhemorrhages and/or cognitive impairment. Very little is known about the mechanisms causing CAA-related degeneration of cerebral vascular cells. The Dutch E22Q familial amyloid-β (Aβ) variant is primarily associated with CAA, and manifests clinically with severe cerebral hemorrhages. Objective: We aimed to determine the molecular mechanisms causing apoptosis of cerebral endothelial cells in the presence of wild-type Aβ40 or its vasculotropic E22Q variant. Methods: We challenged human brain microvascular endothelial cells with both Aβ variants, and studied the apoptotic pathways triggered by these peptides. Results: Caspase-mediated apoptotic pathways were elicited by both peptides within time frames correlating with their aggregation properties and formation of oligomeric/protofibrillar assemblies. Our data revealed a primary activation of caspase-8 (typically triggered by death receptors) with secondary engagement of caspase-9, with cytochrome C and apoptosis-inducing factor release from the mitochondria, suggesting the independent or synergistic engagement of extrinsic and intrinsic apoptotic mechanisms. Conclusion: Our data demonstrate the induction of caspase-8- and caspase-9-dependent mitochondrial-mediated apoptotic pathways by Aβ oligomers/protofibrils in vascular cells, likely implicating a primary activation of death receptors.

© 2011 S. Karger AG, Basel


  1. Revesz T, Holton JL, Lashley T, Plant G, Frangione B, Rostagno A, Ghiso J: Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies.Acta Neuropathol 2009;118:115–130.
  2. Zlokovic BV: The blood brain barrier in health and chronic neurodegenerative disorders. Neuron 2008;57:178–201.
  3. Levy E, Carman MD, Fernandez Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Frangione B: Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 1990;248:1124–1126.
  4. Walsh DM, Selkoe DJ: A beta oligomers – A decade of discovery. J Neurochem 2007;101:1172–1184.
  5. Ono K, Condron MM, Teplow DB: Structure-neurotoxicity relationships of amyloid betaprotein oligomers. Proc Natl Acad Sci USA 2009;106:14745–14750.
  6. Fossati S, Cam J, Meyerson J, Mezhericher E, Romero IA, Couraud PO, Weksler BB, Ghiso J, Rostagno A: Differential activation of mitochondrial apoptotic pathways by vasculotropic amyloid-beta variants in cells composing the cerebral vessel walls. FASEB J 2010;24:229–241.
  7. Miravalle L, Tokuda T, Chiarle R, Giaccone G, Bugiani O, Tagliavini F, Frangione B, Ghiso J: Substitutions at codon 22 of Alzheimer’s Aβ peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J Biol Chem 2000;275:27110–27116.
  8. Weksler BB, Subileau EA, Perrière N, Charneau P, Holloway K, Leveque M, Tricoire-Leignel H, Nicotra A, Bourdoulous S, Turowski P, Male DK, Roux F, Greenwood J, Romero IA, Couraud PO: Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J 2005;19:1872–1874.

Article / Publication Details

First-Page Preview
Abstract of Paper

Received: June 30, 2011
Accepted: September 02, 2011
Published online: December 07, 2011
Issue release date: April 2012

Number of Print Pages: 5
Number of Figures: 2
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.