| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, May 10, 1996, and in revised form, September 18, 1996)
From the Departments of ¶ Pathology, " Neurology,
and In hereditary cerebral hemorrhage with
amyloidosis, Dutch type (HCHWA-D), a genetic variant (E22Q) of amyloid
Volume 271, Number 50,
Issue of December 13, 1996
pp. 32185-32191
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
in Hereditary Cerebral Hemorrhage with
Amyloidosis, Dutch Type
IMPLICATIONS FOR THE ROLE OF AMYLOID-
1-42 IN ALZHEIMER'S
DISEASE
,
,
and
Pharmacology, New York University Medical Center, New
York, New York 10016 and the 
Department of Neurology, Gunma
University School of Medicine, Gunma 371, Japan
(A) accumulates predominantly in the small vessels of
leptomeninges and cerebral cortex, leading to fatal strokes in the
fifth or sixth decade of life. A deposition in the neuropil occurs
mainly in the form of preamyloid, Congo red negative deposits, while
mature neuritic plaques and neurofibrillary tangles, hallmark lesions
in Alzheimer's disease (AD), are characteristically absent. A recent
hypothesis regarding the pathogenesis of AD states that A extending
to residues 42-43 (as opposed to shorter species) can seed amyloid
formation and trigger the development of neuritic plaques followed by
neuronal damage in AD. We characterized biochemically and
immunohistochemically A from three cases of HCHWA-D to determine its
length in vascular and parenchymal deposits. Mass spectrometry of
formic acid-soluble amyloid, purified by size-exclusion gel
chromatography, showed that A 1-40 and its carboxyl-terminal
truncated derivatives were the predominant forms in leptomeningeal and
cortical vessels. A 1-42 was a minor component in these amyloid
extracts. Immunohistochemistry with antibodies S40 and S42, specific
for A ending at Val-40 or Ala-42, respectively, were consistent with
the biochemical data from vascular amyloid. In addition, parenchymal
preamyloid lesions were specifically stained with S42 and were not
labeled by S40, in agreement with the pattern reported for AD, Down's syndrome, and aged dogs. Our results suggest that in HCHWA-D the carboxyl-terminal A heterogeneity is due to limited proteolysis in vivo. Moreover, they suggest that A species ending at
Ala-42 may not be critical for the seeding of amyloid formation and the development of AD-like neuritic changes.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. D. Van Vickle, C. L. Esh, I. D. Daugs, T. A. Kokjohn, W. M. Kalback, R. L. Patton, D. C. Luehrs, D. G. Walker, L.-F. Lue, T. G. Beach, et al. Tg-SwDI Transgenic Mice Exhibit Novel Alterations in A{beta}PP Processing, A{beta} Degradation, and Resilient Amyloid Angiopathy Am. J. Pathol., August 1, 2008; 173(2): 483 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Llovera, M. de Tullio, L. G. Alonso, M. A. Leissring, S. B. Kaufman, A. E. Roher, G. de Prat Gay, L. Morelli, and E. M. Castano The Catalytic Domain of Insulin-degrading Enzyme Forms a Denaturant-resistant Complex with Amyloid {beta} Peptide: IMPLICATIONS FOR ALZHEIMER DISEASE PATHOGENESIS J. Biol. Chem., June 20, 2008; 283(25): 17039 - 17048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tamaki, S. Ohtsuki, and T. Terasaki Insulin Facilitates the Hepatic Clearance of Plasma Amyloid beta-Peptide (1 40) by Intracellular Translocation of Low-Density Lipoprotein Receptor-Related Protein 1 (LRP-1) to the Plasma Membrane in Hepatocytes Mol. Pharmacol., October 1, 2007; 72(4): 850 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tomidokoro, T. Lashley, A. Rostagno, T. A. Neubert, M. Bojsen-Moller, H. Braendgaard, G. Plant, J. Holton, B. Frangione, T. Revesz, et al. Familial Danish Dementia: CO-EXISTENCE OF DANISH AND ALZHEIMER AMYLOID SUBUNITS (ADan AND A{beta}) IN THE ABSENCE OF COMPACT PLAQUES J. Biol. Chem., November 4, 2005; 280(44): 36883 - 36894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Koppaka, C. Paul, I. V. J. Murray, and P. H. Axelsen Early Synergy between A{beta}42 and Oxidatively Damaged Membranes in Promoting Amyloid Fibril Formation by A{beta}40 J. Biol. Chem., September 19, 2003; 278(38): 36277 - 36284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Morelli, R. Llovera, S. A. Gonzalez, J. L. Affranchino, F. Prelli, B. Frangione, J. Ghiso, and E. M. Castano Differential Degradation of Amyloid {beta} Genetic Variants Associated with Hereditary Dementia or Stroke by Insulin-degrading Enzyme J. Biol. Chem., June 20, 2003; 278(26): 23221 - 23226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Munoz, C. Opazo, G. Gil-Gomez, G. Tapia, V. Fernandez, M. A. Valverde, and N. C. Inestrosa Vitamin E But Not 17beta -Estradiol Protects against Vascular Toxicity Induced by beta -Amyloid Wild Type and the Dutch Amyloid Variant J. Neurosci., April 15, 2002; 22(8): 3081 - 3089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lalowski, A. Golabek, C. A. Lemere, D. J. Selkoe, H. M. Wisniewski, R. C. Beavis, B. Frangione, and T. Wisniewski The "Nonamyloidogenic" p3 Fragment (Amyloid beta 17-42) Is a Major Constituent of Down's Syndrome Cerebellar Preamyloid J. Biol. Chem., December 27, 1996; 271(52): 33623 - 33631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. McLaurin, R. Golomb, A. Jurewicz, J. P. Antel, and P. E. Fraser Inositol Stereoisomers Stabilize an Oligomeric Aggregate of Alzheimer Amyloid beta Peptide and Inhibit Abeta -induced Toxicity J. Biol. Chem., June 9, 2000; 275(24): 18495 - 18502. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
