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PMID: 10550301 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death.

The American journal of pathology ·Vol. 155 ·No. 5 ·1999-11-00 ·Pages 1459-66

Stadelmann C, Deckwerth TL, Srinivasan A, Bancher C, Brück W, Jellinger K, Lassmann H

Abstract

Neuronal loss is prominent in Alzheimer's disease (AD), and its mechanisms remain unresolved. Apoptotic cell death has been implicated on the basis of studies demonstrating DNA fragmentation and an up-regulation of proapoptotic proteins in the AD brain. However, DNA fragmentation in neurons is too frequent to account for the continuous neuronal loss in a degenerative disease extending over many years. Furthermore, the typical apoptotic morphology has not been convincingly documented in AD neurons with fragmented DNA. We report the detection of the activated form of caspase-3, the central effector enzyme of the apoptotic cascade, in AD and Down's syndrome (DS) brain using an affinity-purified antiserum. In AD and DS, single neurons with apoptotic morphology showed cytoplasmic immunoreactivity for activated caspase-3, whereas no neurons were labeled in age-matched controls. Apoptotic neurons were identified at an approximate frequency of 1 in 1100 to 5000 neurons in the cases examined. Furthermore, caspase-3 immunoreactivity was detected in granules of granulovacuolar degeneration. Our results provide direct evidence for apoptotic neuronal death in AD with a frequency compatible with the progression of neuronal degeneration in this chronic disease and identify autophagic vacuoles of granulovacuolar degeneration as possible means for the protective segregation of early apoptotic alterations in the neuronal cytoplasm.

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/enzymology,pathology Apoptosis Caspase 3 Caspases/metabolism Cytoplasmic Granules/enzymology,pathology DNA Fragmentation Enzyme Activation Female Humans Male Middle Aged Neurons/enzymology,pathology,ultrastructure
Chemicals
CASP3 protein, human Caspase 3 Caspases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Stadelmann C
Department of Neuroimmunology, University of Vienna, Vienna, Austria.
Deckwerth T L
Srinivasan A
Bancher C
Brück W
Jellinger K
Lassmann H
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65460-0
Published
1999-11-00
Pages
1459-66
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1866960
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65460-0 PMC Full Text View journal details
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