Neuroinflammatory Mechanisms in Alzheimer’s Disease Basic and Clinical Research

265 Pages·2001·5.43 MB·English

by  Harry E. Peery

Progress in Inflammation Research
Series Editor
Prof. Dr. Michael J. Parnham
PLiVA
Research Institute
Prilaz baruna Filipovica25
10000Zagreb
Croatia
Forthcomingtitles:
Disease-modifying Therapy in Vasculitides, C.G.M. Kallenberg, JW. Cohen Tervaert
(Editors), 2001
MechanismsandMediators ofNeuropathicPain, A.B. Malmberg, S.R. ChapIan (Editors),
2001
Inflammation andStroke, G. Feuerstein (Editor), 2001
NMDA AntagonistsasPotential AnalgesicDrugs, R.G. Hill, D.J.S. Sirinathsinghji (Editors),
2001
The Hereditary BasisofAllergicDisorders, J.Holioway, S. Holgate (Editors), 2001
Migraine: ANeuroinflammatoryDisease?, E.L.H. Spierings, M. Sanchezdel Rio (Editors),
2002
(Already published titles see lastpage)
Neuroinflammatory Mechanisms in Alzheimer's
Disease
Basic and Clinical Research
Joseph Rogers
Editor
Springer Basel AG
Editor
Dr. Joseph Rogers
Sun Health Research Institute
10 515 West Santa Fe Drive
Sun City, AZ 85372
USA
A CIP catalogue record for this book is available from the Library of Congress, Washington D.C., USA
Deutsche 8ibliothek Cataloging-in-Publication Data
Neuroinflammatory mechanisms in Alzheimer's disease : basic and clinical research /
Joseph Rogers ed .. -Basel ; Boston; Berlin: Birkhauser, 2001
(Progress in inflammation research)
ISBN 978-3-0348-9529-3 ISBN 978-3-0348-8350-4 (eBook)
DOI 10.1007/978-3-0348-8350-4
The publisher and editor can give no guarantee for the information on drug dosage and administration contained in
this publication. The respective user must check its accuracy by consulting other sources of reference in each individual
case.
The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that
they are exempt from the relevant protective laws and regulations or free for general use.
This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is concerned,
specifically the rights of translation, reprinting, re-use of iIIustrations, recitation, broadcasting, reproduction on micro
films or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must
be obtained.
© 2001 Springer Basel AG
Originally published by Birkhauser Verlag in 2001
Softcover reprint of the hardcover 1s t edition 2001
Printed on acid-free paper produced from chlorine-free pulp. TCF =
Cover design: Markus Etterich, Basel
Cover illustration: Accumulation of astrocytes in neuritic plaques in an AD brain (p. 95ff).
ISBN 978-3-0348-9529-3
987654321
Contents
List of contributors . vii
Preface........................................................................... xi
Basic Research Overview
Harry E. Peery, Ron W StrohmeyerandJoseph Rogers
Cellular and molecular mechanisms of Alzheimer's disease inflammation 3
Clinical Research Overview
Patrick L. McGeer, Michael Schulzerand Edith G. McGeer
Anti-inflammatory agents as possible protective factors for
Alzheimer's disease: Analysis of relevant epidemiological studies . 53
Topics ofSpecial Interest
Robert Veerhuis, Freek L. Van Muiswinkel, C. Erik Hack
and Piet Eikelenboom
Role and regulation of early complement activation products in
Alzheimer's disease.. ............... . . .......... 67
Bonnie M. Bradt, Stephen A. O'Barr, Jack X. Yu and Neil R. Cooper
Complement mediator systems in Alzheimer's disease. 89
ScottD. Webster
Amyloid ~ peptide interactions with the classical pathway ofcomplement .... 105
Harald Hampel, Michael Scheloske and Andreas Haslinger
Physiology and biochemistry ofthe interleukin-6 receptor complex~
Implications for CNS disorders and Alzheimer's disease 121
Ikuo Tooyama
Interactions ofa2-macroglobulin and amyloid ~ peptide 145
vv.
Steven Barger
Proinflammatory actions of derivatives ofthe ~ amyloid precursor protein ..... 155
Douglas G. Walker, Lih-Fen Lue, Andis Klegeris andPatrick L. McGeer
The involvement of glial cell-derived reactive oxygen and nitrogen species
in Alzheimer's disease 173
Giulio Maria Pasinetti
The role ofcydooxygenase in Alzheimer's disease neurodegeneration .. ... 197
Ian R.A. Mackenzie
Microglia . . 209
Haruhiko Akiyama
Neurons . .............225
Caleb E. Finch and Valter D. Longo
The gero-inflammatory manifold . ..237
Index 257
List of contributors
Haruhiko Akiyama, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya
ku, Tokyo, 156-8585,Japan; e-mail: [email protected]
Steven W. Barger, Geriatric Research Education Clinical Center, Central Arkansas
Veterans Healthcare System, Little Rock, AR 72205, USA;
e-mail: [email protected]
Bonnie M. Bradt, Department of Internal Medicine, University of California Davis
Medical Center, 1508 Alhambra Blvd., Sacramento, CA 95816, USA;
e-mail: [email protected]
Neil R. Cooper, DepartmentofImmunology, The Scripps Research Institute, 10550
North Torrey Pines Road, LaJolla, CA 92037, USA; e-mail: [email protected]
Piet Eikelenboom, Research Institute Neurosciences Vrije Universiteit, Department
of Psychiatry, PCA Valeriuskliniek, Valeriusplein 9, 1075 BG Amsterdam, The
Netherlands; e-mail: [email protected]
Caleb E. Finch, Andrus Gerontology Center and Department ofBiological Sciences,
University ofSouthern California, Los Angeles, CA 90089-0191, USA;
e-mail: [email protected]
C. Erik Hack, Department of Autoimmune Diseases, Central Laboratory of the
Netherlands Red Cross Bloodtransfusion Service, Plesmanlaan 125, 1066 CX Ams
terdam, The Netherlands; e-mail: [email protected]
Harald Hampel, Dementia Research Section, Department of Psychiatry, Ludwig
Maximilian University, Nussbaumstr. 7, 80336 Munich, Germany;
e-mail: [email protected]
Andreas Haslinger, Dementia Research Section, Department of Psychiatry, Ludwig
Maximilian University, Nussbaumstr. 7,80336 Munich, Germany
Listofcontributors
Andis Klegeris, Kinsmen LaboratoryofNeurological Research, UniversityofBritish
Columbia, 2255 Wesbrook Mall, Vancouver, B.C., V6T IZ3 Canada;
e-mail: [email protected]
Valter D. Longo, Andrus Gerontology Center and Department of Biological Sci
ences, University of Southern California, Los Angeles, CA 90089-0191, USA;
e-mail: [email protected]
Lih-Fen Lue, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City,
AZ 85351, USA; e-mail: [email protected]
Ian R.A. Mackenzie, Department ofPathology and Laboratory Medicine, Universi
ty ofBritish Columbia, Vancouver, B.C., V6T 2B5 Canada;
e-mail: [email protected]
Edith G. McGeer, Kinsmen Laboratory of Neurological Research, Department of
Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B.C.,
V6T 1Z3 Canada; e-mail: [email protected]
Patrick L. McGeer, Kinsmen Laboratory of Neurological Research, Department of
Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B.C.,
V6T 1Z3 Canada; e-mail: [email protected]
StephenA. O'Barr, College ofPharmacy,Western UniversityofHealth Sciences, 309
East Second Street, Pomona, CA 91766-1854, USA
Giulio Maria Pasinetti, Neuroinflammation Research Laboratories, Department of
Psychiatry, MountSinaiSchool ofMedicine, One Gustave L. LevyPlace,New York,
NY 10029, USA; e-mail: [email protected]
Harry E. Peery, Department of Pharmacology and Toxicology, College of Pharma
cy, Arizona Health Sciences Center, University ofArizona, Tucson, AZ 85721, USA
Joseph Rogers, Sun Health Research Institute, 10515WestSanta Fe Drive, Sun City,
AZ 85351, USA; e-mail: [email protected]
Michael Scheloske, Dementia Research Section, Department ofPsychiatry, Ludwig
Maximilian University, Nussbaumstr. 7, 80336 Munich, Germany
Michael Schulzer, Kinsmen Laboratory of Neurological Research, Departments of
Medicine and Statistics, University ofBritish Columbia, 2255 Wesbrook Mall, Van
couver, B.C., V6T 1Z3 Canada; e-mail: [email protected]
viii
Listofcontributors
RonW. Strohmeyer, SunHealth Research Institute, 10515West SantaFeDrive, Sun
City, AZ 85351, USA
Ikuo Tooyama, Molecular Neuroscience Research Center, Shiga University ofMed
ical Science, Otsu 520-2192,Japan; e-mail: [email protected]
Freek L. Van Muiswinkel, Research Institute Neurosciences Vrije Universiteit,
DepartmentofPharmacology,Van der Boechorststraat7, 1081 BTAmsterdam,The
Netherlands; e-mail: [email protected]
RobertVeerhuis, Research Institute NeurosciencesVrije Universiteit, Departmentof
Pathology, De Boe1elaan 1117, 1081 HV Amsterdam, The Netherlands;
e-mail: [email protected]
Douglas G. Walker, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun
City, AZ 85351, USA; e-mail: [email protected]
Scott D. Webster, Department of Molecular Biology and Biochemistry, 3205 Bio
logical Sciences II, University of California, Irvine, CA 92697, USA;
e-mail: [email protected]
Jack X. Yu, Department of Immunology, The Scripps Research Institute, 10550
North Torrey Pines Road, La Jolla, CA 92037, USA
ix
Preface
Research into inflammatory mechanisms that maycause damage to the Alzheimer's
disease (AD) brain has now been ongoing for nearly two decades. Some two dozen
clinical studies have strongly suggested that conventional anti-inflammatory drugs
may be useful to delay the onset or slow the progression ofthe disorder. Moreover,
virtually all the major systems ofthe innate immune response appear to be present,
and most are upregulated, in pathologically-vulnerable regions of the AD brain.
These new findings are described in this volume - first in overview form, followed
by chapters on topics ofspecial interest.
In many ways, to understand AD brain inflammation, one need only review a
texton peripheral inflammation biology, leavingoutthe chapters on humoral medi
ators and substituting microglia for macrophages. In several other key respects,
however, AD brain inflammation is unique, due primarily to idiosyncratic interac
tions of inflammatory mediators and mechanisms with classical AD pathology:
amyloid ~ peptide (A~) deposits and neurofibrillary tangles (NFTs). Forthis reason,
some key concepts about the inflammation that occurs in AD may warrant discus
sion in preparation for the more detailed chapters that follow.
AD brain inflammation does not appear to be humorally mediated. Although
CD4- and CD8-immunoreactiveT cells areeasilydemonstrated in the AD brain, no
rigorously measured quantitative difference with T cells in the non-demented elder
ly (ND) brain has been reported. Immunoreactivity for antibodies is also similar in
AD and ND cortical samples, and the staining itself is equivocal. Assays for serum
antibodies directed at A~ reveal that approximately halfofAD patients and halfof
ND patients have equivalent, low titers. Bcells and natural killer cells appear to be
absent from the AD brain parenchyma. As negative results, these observations (J.
Rogers, unpublishedobservations) have never been formally reported, butmaywar
rant re-examination in light of the success of a vaccination approach to removing
A~, implying some form of humoral mediation.
The fact that AD inflammation uses innate rather than humoral mechanisms
does notmean that itis unimportant. Neuroimmunology has become progressively
dominated by lymphocyte biology, and remarkable progress has been made thereby