Caspase activation precedes and leads to tangles

Alix de Calignon, Leora M. Fox, Rose Pitstick, George A. Carlson, Brian J. Bacskai, Tara L. Spires-Jones and Bradley T. Hyman ()
Additional contact information
Alix de Calignon: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Leora M. Fox: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Rose Pitstick: McLaughlin Research Institute, Great Falls, Montana 59401, USA
George A. Carlson: McLaughlin Research Institute, Great Falls, Montana 59401, USA
Brian J. Bacskai: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Tara L. Spires-Jones: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Bradley T. Hyman: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

Nature, 2010, vol. 464, issue 7292, 1201-1204

Abstract: Tangled tau: friend or foe? Based largely on evidence from post-mortem examination of brain tissue, it is thought that abnormal fibrillar deposits of tau protein — which when functioning normally acts to stabilize microtubules — cause apoptosis and neurodegeneration in Alzheimer's disease and tau-related frontotemporal dementia. Now in vivo multiphoton imaging of these neurofibrillary tangles in transgenic mice overexpressing a human tau gene reveals a rather different scenario. Caspase activation — a known marker for apoptosis — is the first abnormality observed, preceding tangle formation by hours to days. Rather than suffering cell death, neuronal cells bearing tangles appear to be long-lived, and caspase activity subsides. It is therefore possible that soluble tau, rather than fibrillar tau, is causing neurodegeneration. As to the relevance of this work to the value of 'tangle-busting' drugs in countering neurodegeneration, much depends on whether neurofibrillary tangles are a protective factor, an irrelevance to the disease, or are associated with slow-acting neurotoxicity.

Date: 2010
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature08890 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:464:y:2010:i:7292:d:10.1038_nature08890

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature08890

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().