Alterations in the Neuronal Cytoskeleton in Alzheimer Disease

229 Pages·1988·14.18 MB·English

by  Steven S. M. Chin

Alterations in the
Neuronal Cytoskeleton in
Alzheimer Disease
ADVANCES IN BEHA VIORAL BIOLOGY
Editorial Board
Jan Bures Institute of Physiology, Prague, Czechoslovakia
Irwin Kopin National Institute of Mental Health, Bethesda, Maryland
Bruce McEwen Rockefeller University, New York, New York
James McGaugh University of California, Irvine, California
Karl Pribram Stanford University School of Medicine, Stanford, California
Jay Rosenblatt Rutgers University, Newark, New Jersey
Lawrence Weiskrantz University of Oxford, Oxford, England
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ALZHEIMER DISEASE
Edited by George Perry
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Alterations in the
Neuronal Cytoskeleton in
Alzheimer Disease
Edited by
GEORGE PERRY
Case Western Reserve University
Cleveland, Ohio
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Alterations in the neuronal cytoskeleton in Alzheimer disease.
(Advances in behavioral biology; v. 34)
Based on proceedings of a symposium held Dec. 7, 1986 in Washington,
D.C.
Includes bibliographies and index.
1. Alzheimer's disease-Pathophysiology-Congresses. 2. Cytoskeletal pro
teins-Congresses. 3. Cytoplasmic filaments-Congresses. I. Perry, George. 11.
Series. [DNLM: 1. Alzheimer's Disease-pathology-congresses. 2. Cytos
keletons - pathology -congresses. 3. Neurofibrils - pathology -congresses.
WM 220 A466 19B6J
RC523.A37 1987 616.8'3 87-29256
ISBN-13: 978-1-4612-8920-3 e-ISBN-13: 978-1-4613-1657-2
001: 10.1007/978-1-4613-1657-2
Based on proceedings of a symposium on Reorganization of the Neuronal
Cytoskeleton in Aging, held December 7. 1986, in Washington, D.e.
© 1987 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1987
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
TO THE MEMORY OF MY FATHER
PREFACE
The neuronal cytoskeleton is a complex structure responsive to both
intrinsic and extrinsic factors. Defined populations of neurons in the
brains of patients with Alzheimer and several other neurodegenerative
diseases contain abnormal filamentous accumulations which share elements
with the cytoskeleton. Although there is a general consensus that these
abnormal filaments do contain cytoskeletal elements, much debate remains
regarding which cytoskeletal elements are incorporated and whether the
cytoskeletal rearrangement is primary or secondary to other cellular
changes.
In this book these questions are addressed in a historical perspect
ive in light of new data that allows the reinterpretation of previously
reported results. Contributions are based on many of the major tech
niques of modern biology including biochemistry, molecular biology,
electron microscopy and immunocytochemistry.
In the view of the editor, this volume is being written at a time
when our understanding of the cytopathology of Alzheimer disease is
moving from predominantly descriptive to both analytical and mechanistic.
I hope that this contribution will provide impetus to speed this transi
tion.
George Perry
Cleveland, Ohio
vii
ACKNOWLEDGEMENT
The support of the Fidia Pharmaceutic Corporation for the computer
generated color figure on page 65 is gratefully acknowledged.
viii
CONTENTS
Neurofilaments: A Review and Update 1
S.S.M. Chin and R.K.H. Liem
The Phosphorylation of the Microtubule-associated Tau
Proteins •••••••••••••••• 25
J. Baudier and R.D. Cole
Human Amyloidosis and In Vitro Formation of Alzheimer Amyloid
Fibrils • ••• • • • • • • • • • • • • • • 33
E.M. Castano and B. Frangione
Cloning of Neurofibrillary Tangle-related Genes • • • • • • • • •• 45
K.S. Kosik and R. Neve
Ubiquitin in Alzheimer and Other Neurodegenerative Diseases. • •. 53
G. Perry, V. Manetto, and P. Mulvihill
Neuronal Fibrillar Cytoskeleton and Endomembrane System
Organization in Alzheimer's Disease ••• 61
M. Ellisman, R. Ranganathan, T. Deerinck, S. Young,
R. Terry, and S. Mirra
Transformation of the Neurofilamentous Network Components
into PHF-like Strands and PHF Paracrystals 75
J. Metuzals, Y. Robitaille, S. Houghton, S. Gauthier,
and R. Leblanc
Intraneuronal and Extracellular Filaments in the Pathogenesis
of Alzheimer's Disease ••••••••••••••• 97
D.J. Selkoe
Alterations of the Neuronal Cytoskeleton in Alzheimer's
Disease and Related Conditions ••••• 109
K. Iqbal, I. Grundke-Iqbal, H.M. Wisniewski
Alterations of the Neurofilament-microtubule Network
in Alzheimer Disease And Other Neurodegenerative
Disorders • • • • • • • • • • • • • • • • • • • • 137
G. Perry, V. Manetto, M. Onorato, M. Weiss, p. Mulvihill,
p. Galloway, M. Tabaton, L. Autilio-Gambetti, and
p. Gambetti
ix
Immunochemical Studies of the Relationship Between the
Neuronal Cytoskeleton and Neurofibrillary Tangles 151
D.P. Hue, J.p. Brion, P.A. Robinson, and B.H. Anderton
Monoclonal Antibodies Show Cross-reactivity of Alzheimer
Neurofibrillary Tangles and Heat-stable Microtubule-
associated Proteins • • • • • • • • •• •• • • • 165
D.W. Dickson, H. Ksiezak-Reding, A. Crowe, and S.H. Yen
An Immunocytochemical Comparative Analysis of Tau in
Neurodegenerative Diseases 181
N.J. Pollock, S.S. Mirra, and J.G. Wood
Cytoskeletal Abnormalities in Parkinson's Disease 191
J.E. Goldman
Microfilament Involvement in Hirano Body Formation 199
p. Galloway and G. Perry
Contributors 211
Index • • • • 215
x
NEUROFILAMENTS: A REVIEW AND UPDATE
Steven S.M. Chin and Ronald K.H. Liem
Department of Pharmacology
New York University School of Medicine
New York, N.Y.
INTRODUCTION
For decades neuroanatomists have been familiar with a
distinctive fibrillar appearance of large mammalian axons after
treatment of nervous tissue with various silver stains. These
structures were aptly referred to as "neurofibrils." It was
only relatively recently through combined efforts utilizing
electron microscopic, biochemical, and immunological
methodologies that these well-known structures have been more
precisely defined and characterized. Today we refer to these
"neurofibrils" as neurofilaments. The goal of this chapter is
to review our current knowledge and understanding of
neurofilaments in the context of normal cell function.
MORPHOLOGY
Electron microscopic examination of ultra-thin sections
taken through large mammalian axons clearly reveal an abundance
of electron-dense filaments measuring from 7 to 15 nanometers
(nm) in diameterl . These neurofilaments (NF) are easily
distinguished from the larger (25-30nm) microtubules. Ultra
thin sectioned material also reveal a finer fibrillar, whisker
like material which seems to cross link neurofilaments to each
other as well as to microtubules. This feature is unique among
the lOnm or intermediate filaments (IF) of which the
neurofilaments are a member. Studies using quick-freeze, deep
etching techniques have confirmed the existence of these
crosslinkers (4-6nm in diameter and 20-50nm in length) in
~2,3. High magnification analysis of cross-sectioned
neurofilaments reveal an electron-lucent core measuring
approximately 3nm in width. Metal-shadowed preparations of
isolated and re-assembled neurofilaments have consistently
demonstrated a 2lnm axial periodicity which has been directly
correlated with the prevailing model of IF structure (see
below)4,5.