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

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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

DOI 10.1016/s0002-9440(10)63317-2PMC PMC1618555

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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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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.
ORCID: Albrecht, Steffen
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)
DOI: 10.1016/s0002-9440(10)63317-2
PMC: PMC1618555
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Active Caspase-6 and Caspase-6-Cleaved Tau in Neuropil Threads, Neuritic Plaques, and Neurofibrillary Tangles of Alzheimer's Disease

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