Codistribution of Amyloid ß Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype

Vol. 66 No. 10, October 2009

Codistribution of Amyloid ß Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype

Nupur Ghoshal, MD, PhD; Ignazio Cali, MS; Richard Justin Perrin, MD, PhD; S. Andrew Josephson, MD; Ning Sun, MD, PhD; Pierluigi Gambetti, MD; John Carl Morris, MD

Arch Neurol. 2009;66(10):1240-1246.

Background Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid ß (Aß) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation.

Objective To characterize a family with CJD in which Aß plaques codistribute with spongiform degeneration.

Design Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.

Setting Alzheimer disease research center.

Participants Two generations of a family.

Main Outcome Measures Clinical, biochemical, and neuropathologic observations in 2 generations of a family.

Results In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Aß plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Aß plaques were present in the APOE 4 carrier but not in the APOE 4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children.

Conclusions To our knowledge, this is the first description of Aß plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Aß formation and that Aß pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrPE200K may result in increased Aß deposition.

Author Affiliations: Department of Neurology and Alzheimer's Disease Research Center (Drs Ghoshal, Perrin, and Morris) and Division of Neuropathology, Department of Pathology and Immunology (Drs Perrin and Morris), Washington University School of Medicine, St Louis, Missouri; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio (Mr Cali and Dr Gambetti); Department of Neurology, University of California, San Francisco (Dr Josephson); and DuPage Neurological Associates, Willowbrook, Illinois (Dr Sun).

http://archneur.ama-assn.org/cgi/content/short/66/10/1240



Saturday, October 31, 2009

Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients

http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html




SEAC OCTOBER 2009

. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility

http://www.seac.gov.uk/pdf/hol-response091008.pdf


Thursday, February 26, 2009

'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???

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


CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES

1. 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; and

iii) 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.

93/01.05/4.1tss



http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf




Regarding Alzheimer's disease

(note the substantial increase on a yearly basis)



http://web.archive.org/web/20010305222847/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://web.archive.org/web/20010305223234/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://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf



http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf




BSE101/1 0136

IN CONFIDENCE

5 NOV 1992

CMO From: Dr J S Metters DCMO 4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES




http://web.archive.org/web/20010305223143/www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf




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




http://web.archive.org/web/20010305222847/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.html



re-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



Monday, October 12, 2009

SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009



http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html





Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD



http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html





TSS