Cited by 288Alzheimer's disease research and treatmentsCell death mechanisms and regulationNeuroinflammation and Neurodegeneration Mechanisms

Active Caspase-6 and Caspase-6-Cleaved Tau in Neuropil Threads, Neuritic Plaques, and Neurofibrillary Tangles of Alzheimer's Disease

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Guo, Huishan, Albrecht, Steffen, Bourdeau, Martine, Petzke, Tracy, Bergeron, Catherine, LeBlanc, Andrea C.·2004·The American Journal of Pathology

Abstract

Previously, we have shown that caspase-6 but not caspase-3 is activated by serum deprivation and induces a protracted cell death in primary cultures of human neurons (LeBlanc AC, Liu H, Goodyer C, Bergeron C, Hammond J: Caspase-6 role in apoptosis of human neurons, amyloidogenesis and Alzheimer's disease. J Biol Chem 1999, 274:23426-23436 and Zhang Y, Goodyer C, LeBlanc A: Selective and protracted apoptosis in human primary neurons microinjected with active caspase-3, -6, -7, and -8. J Neurosci 2000, 20:8384-8389). Here, we show with neoepitope antibodies that the p20 subunit of active caspase-6 increases twofold to threefold in the affected temporal and frontal cortex but not in the unaffected cerebellum of Alzheimer's disease brains and is present in neurofibrillary tangles, neuropil threads, and the neuritic plaques. Furthermore, a neoepitope antibody to caspase-6-cleaved Tau strongly detects intracellular tangles, extracellular tangles, pretangles, neuropil threads, and neuritic plaques. Immunoreactivity with both antibodies in pretangles indicates that the caspase-6 is active early in the pathogenesis of Alzheimer's disease. In contrast to the nuclear and cytosolic localization of active caspase-6 in apoptotic neurons of fetal and adult ischemic brains, the active caspase-6 in Alzheimer's disease brains is sequestered into the tangles or neurites. The localization of active caspase-6 may strongly jeopardize the structural integrity of the neuronal cytoskeletal system leading to inescapable neuronal dysfunction and eventual cell death in Alzheimer's disease neurons. Our results suggest that active caspase-6 is strongly implicated in human neuronal degeneration and apoptosis.

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  1. Stadelmann C, Deckwerth T, Srinivasan A, Bancher C, Bruck W, Jellinger K, Lassmann H: Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzhei- mer's disease. Am J Pathol 1999, 155:1459 -1466

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Authors
Guo, H., Albrecht, S., Bourdeau, M., Petzke, T., Bergeron, C., & LeBlanc, A. C.
Affiliations
  • Jewish General Hospital (CA)
  • University of Toronto (CA)
Corresponding author
LeBlanc, Andrea C.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2004-08
Volume
165
Issue
2
Pages
523-531
ISSN
0002-9440 (ISSN-L)
OpenAlex
W1997426613
Cited by
287
References
32
Citations by year
2026: 4 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 8 · 2021: 21 · 2020: 11 · 2019: 16 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 11 · 2013: 19 · 2012: 19
FWCI
6.78
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • McGill University
  • National Institutes of Health (1r03mh040965-01)
  • National Institute of Neurological Disorders and Stroke (NS/MH40965)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
caspase-6, Alzheimer's disease, neurofibrillary tangles, neuropil threads, neuritic plaques, neuronal apoptosis, tau cleavage, neurodegeneration, caspase-3
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Cell Nucleus, Cerebellum, Cerebral Cortex, Cytosol, Humans, Middle Aged, Neurofibrillary Tangles, tau Proteins, Apoptosis, Neuropil Threads, Caspases, Caspase 6, Plaque, Amyloid

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