Transmission and spreading of tauopathy in transgenic mouse brain

Letter abstract

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Nature Cell Biology Published online: 7 June 2009 doi:10.1038/ncb1901

Transmission and spreading of tauopathy in transgenic mouse brain

Florence Clavaguera1, Tristan Bolmont2, R. Anthony Crowther3, Dorothee Abramowski4, Stephan Frank1, Alphonse Probst1, Graham Fraser3, Anna K. Stalder5, Martin Beibel4, Matthias Staufenbiel4, Mathias Jucker2, Michel Goedert3,6 & Markus Tolnay1,6

Top of pageHyperphosphorylated tau makes up the filamentous intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease1. In the disease process, neuronal tau inclusions first appear in the transentorhinal cortex from where they seem to spread to the hippocampal formation and neocortex2. Cognitive impairment becomes manifest when inclusions reach the hippocampus, with abundant neocortical tau inclusions and extracellular -amyloid deposits being the defining pathological hallmarks of Alzheimer's disease. An abundance of tau inclusions, in the absence of -amyloid deposits, defines Pick's disease, progressive supranuclear palsy, corticobasal degeneration and other diseases1. Tau mutations cause familial forms of frontotemporal dementia, establishing that tau protein dysfunction is sufficient to cause neurodegeneration and dementia3, 4, 5. Thus, transgenic mice expressing mutant (for example, P301S) human tau in nerve cells show the essential features of tauopathies, including neurodegeneration and abundant filaments made of hyperphosphorylated tau protein6, 8. By contrast, mouse lines expressing single isoforms of wild-type human tau do not produce tau filaments or show neurodegeneration7, 8. Here we have used tau-expressing lines to investigate whether experimental tauopathy can be transmitted. We show that injection of brain extract from mutant P301S tau-expressing mice into the brain of transgenic wild-type tau-expressing animals induces assembly of wild-type human tau into filaments and spreading of pathology from the site of injection to neighbouring brain regions.



Department of Neuropathology, Institute of Pathology, University of Basel, Basel, Switzerland. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. MRC Laboratory of Molecular Biology, Cambridge, UK. Novartis Institutes for Biomedical Research, Basel, Switzerland. Neurology and Neurobiology, University Hospital, Basel, Switzerland. These authors contributed equally to this work Correspondence to: Michel Goedert3,6 e-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000101/!x-usc:mailto:mtolnay@uhbs.ch

Correspondence to: Markus Tolnay1,6 e-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000101/!x-usc:mailto:mg@mrc-lmb.cam.ac.uk



http://www.nature.com/ncb/journal/vaop/ncurrent/abs/ncb1901.html





CJD1/9 0185Ref: 1M51AIN STRICT CONFIDENCETRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES1.

CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.2. Briefly, the meeting agreed that:i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; andiii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.93/01.05/4.1



http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf




Regarding Alzheimer's disease(note the substantial increase on a yearly basis)



http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf




snip...


The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...


snip...



http://www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf




And NONE of this is relevant to BSE?There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.



http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf




???



http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf




BSE101/1 0136IN CONFIDENCE5 NOV 1992CMO From: Dr J S Metters DCMO 4 November 1992TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES



http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf




also, see the increase of Alzheimer's from 1981 to 1986



http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf




Tuesday, August 26, 2008


Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3



http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html




see full text ;



http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html




Alzheimer's and CJD



http://betaamyloidcjd.blogspot.com/




Saturday, March 22, 2008


10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures



http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.htmlre-




Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease



http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html




Sunday, June 7, 2009


ALZHEIMER'S DISEASE IS TRANSMISSIBLE



http://betaamyloidcjd.blogspot.com/2009/06/alzheimers-disease-is-transmissible.html