Monday, August 10, 2015

Detection and Quantification of beta-Amyloid, Pyroglutamyl A beta, and Tau in Aged Canines

Detection and Quantification of [beta]-Amyloid, Pyroglutamyl A[beta], and Tau in Aged Canines.

 

 Schmidt, Franziska; Boltze, Johannes; Jäger, Carsten; Hofmann, Sarah; Willems, Nicole; Seeger, Johannes; Härtig, Wolfgang; Stolzing, Alexandra Less

 

Journal of Neuropathology & Experimental Neurology., Post Author Corrections: August 5, 2015

 

Published Ahead-of-Print

 

 Abstract

 

 Canine cognitive dysfunction syndrome is an age-associated disorder that resembles many aspects of human Alzheimer disease. The characterization of canine cognitive dysfunction syndrome has been restricted to selected laboratory dogs and mongrels, thereby limiting our knowledge of potential breed-related and age-related differences. We examined the brains of 24 dogs from various breeds. The frontal cortex, hippocampus, and entorhinal cortex were investigated. Deposits of [beta]-amyloid (A[beta]) and tau were analyzed phenotypically and quantified stereologically. In all dogs aged 10 years or older, plaques containing pyroglutamyl A[beta] and A[beta]8-17 were detected. Within the ventral hippocampus, significantly more pyroglutamyl A[beta] plaques were deposited in small and medium dogs than in large dogs. Hyperphosphorylated tau with formation of neurofibrillary tangles was observed in 3 animals aged 13 to 15 years. This study provides the first investigation of pyroglutamyl A[beta] in comparison with total A[beta] (as shown by A[beta]8-17 immunoreactivity) in dogs of different breeds, sizes, and ages. Our results indicate that canine cognitive dysfunction syndrome is relatively common among aged canines, thereby emphasizing the relevance of such populations to translational Alzheimer disease research.

 

(C) 2015 by American Association of Neuropathologists, Inc.

 


 

 

HOUND STUDY

 

*** AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease. ***

 

snip...

 


 

DEFRA Department for Environment, Food & Rural Affairs

 

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk

 

GTN: FAX:

 

Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518

 

21 November 2001

 

Dear Mr Singeltary

 

TSE IN HOUNDS

 

Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

 

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

 

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

 

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less

 

critical. For more details see- http://www.bseinquiry, gov.uk/files/yb/1995/06/21005001 .pdf

 

As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

 

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

 

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

 

I hope this is helpful

 

Yours sincerely 4

 

HUGH MCDONAGH BSE CORRESPONDENCE SECTION

 

======================================

 

HOUND SURVEY

 

I am sorry, but I really could have been a co-signatory of Gerald's minute.

 

I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.

 

If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.

 

J W WILESMITH Epidemiology Unit 18 October 1991

 

Mr. R Bradley

 

cc: Mr. G A H Wells

 


 

3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, indentify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.

 


 

TSE in dogs have not been documented simply because OF THE ONLY STUDY, those brain tissue samples were screwed up too. see my investigation of this here, and to follow, later follow up, a letter from defra, AND SEE SUSPICIOUS BRAIN TISSUE SAF's. ...TSS

 


 

TSE & HOUNDS

 

GAH WELLS (very important statement here...TSS)

 

HOUND STUDY

 

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

 

snip...

 


 

76 pages on hound study;

 

snip...

 


 

The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.

 

38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.

 

39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.

 

40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.

 

41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.

 

Histopathological support to various other published MAFF experiments

 

42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).

 


 

It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.

 

snip...

 


 

NEW URL ;

 


 

OR-09: Canine spongiform encephalopathy—A new form of animal prion disease

 

Monique David, Mourad Tayebi UT Health; Houston, TX USA

 

It was also hypothesized that BSE might have originated from an unrecognized sporadic or genetic case of bovine prion disease incorporated into cattle feed or even cattle feed contaminated with prion-infected human remains.1 However, strong support for a genetic origin of BSE has recently been demonstrated in an H-type BSE case exhibiting the novel mutation E211K.2 Furthermore, a specific prion protein strain causing BSE in cattle is believed to be the etiological agent responsible for the novel human prion disease, variant Creutzfeldt-Jakob disease (vCJD).3 Cases of vCJD have been identified in a number countries, including France, Italy, Ireland, the Netherlands, Canada, Japan, US and the UK with the largest number of cases. Naturally occurring feline spongiform encephalopathy of domestic cats4 and spongiform encephalopathies of a number of zoo animals so-called exotic ungulate encephalopathies5,6 are also recognized as animal prion diseases, and are thought to have resulted from the same BSE-contaminated food given to cattle and humans, although and at least in some of these cases, a sporadic and/or genetic etiology cannot be ruled out. The canine species seems to display resistance to prion disease and no single case has so far been reported.7,8 Here, we describe a case of a 9 week old male Rottweiler puppy presenting neurological deficits; and histological examination revealed spongiform vacuolation characteristic of those associated with prion diseases.9 Initial biochemical studies using anti-PrP antibodies revealed the presence of partially proteinase K-resistant fragment by western blotting. Furthermore, immunohistochemistry revealed spongiform degeneration consistent with those found in prion disease and displayed staining for PrPSc in the cortex.

 

Of major importance, PrPSc isolated from the Rottweiler was able to cross the species barrier transmitted to hamster in vitro with PMCA and in vivo (one hamster out of 5). Futhermore, second in vivo passage to hamsters, led to 100% attack rate (n = 4) and animals displayed untypical lesional profile and shorter incubation period.

 

In this study, we show that the canine species might be sensitive to prion disease and that PrPSc isolated from a dog can be transmitted to dogs and hamsters in vitro using PMCA and in vivo to hamsters.

 

If our preliminary results are confirmed, the proposal will have a major impact on animal and public health and would certainly lead to implementing new control measures for ‘canine spongiform encephalopathy’ (CSE).

 

References 1. Colchester AC, Colchester NT. The origin of bovine spongiform encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856-61; PMID:16139661; http:// dx.doi.org/10.1016/S0140-6736(05)67218-2.

 

2. Richt JA, Hall SM. BSE case associated with prion protein gene mutation. PLoS Pathog 2008; 4:e1000156; PMID:18787697; http://dx.doi.org/10.1371/journal. ppat.1000156.

 

3. Collinge J. Human prion diseases and bovine spongiform encephalopathy (BSE). Hum Mol Genet 1997; 6:1699-705; PMID:9300662; http://dx.doi.org/10.1093/ hmg/6.10.1699.

 

4. Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GA, Wilesmith JW. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet Rec 1991; 129:233-6; PMID:1957458; http://dx.doi.org/10.1136/vr.129.11.233.

 

5. Jeffrey M, Wells GA. Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet Pathol 1988; 25:398-9; PMID:3232315; http://dx.doi.org/10.1177/030098588802500514.

 

6. Kirkwood JK, Wells GA, Wilesmith JW, Cunningham AA, Jackson SI. Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros). Vet Rec 1990; 127:418-20; PMID:2264242.

 

7. Bartz JC, McKenzie DI, Bessen RA, Marsh RF, Aiken JM. Transmissible mink encephalopathy species barrier effect between ferret and mink: PrP gene and protein analysis. J Gen Virol 1994; 75:2947-53; PMID:7964604; http://dx.doi.org/10.1099/0022-1317- 75-11-2947.

 

8. Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, et al. Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad Sci U S A 2005; 102:640-5; PMID:15647367; http://dx.doi.org/10.1073/pnas.0408937102.

 

9. Budka H. Neuropathology of prion diseases. Br Med Bull 2003; 66:121-30; PMID:14522854; http://dx.doi.org/10.1093/bmb/66.1.121.

 


 

Monday, March 26, 2012

 

CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE

 


 

Monday, March 8, 2010

 

Canine Spongiform Encephalopathy aka MAD DOG DISEASE

 


 

Friday, August 7, 2015

 

Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

 


 

Wednesday, July 29, 2015

 

Porcine Prion Protein Amyloid or mad pig disease PSE

 


 

Slowly progressive lymphohistiocytic meningoencephalomyelitis in 21 adult cats presenting with peculiar neurological signs

 

Luisa De Risio1, Richard Brown2, Bryn Tennant3, Andy Sparkes4, Lara Matiasek1,5, Alberta de Stefani1, Herbert Weissenböck6 and Kaspar Matiasek1,7

 

Abstract

 

Twenty-one cats presented with a history of slowly progressive neurological signs characterised by a stiff extended tail, behavioural changes, and spastic and ataxic gait. All cats had outdoor access and lived in the same geographical rural area in north-east Scotland. Histological findings were consistent with lymphohistiocytic meningoencephalomyelitis. Immunohistochemistry ruled out 15 pathogens and showed a significant expression of the interferon-inducible Mx protein, suggesting an as yet unidentified infective or environmental immunogenic trigger as the possible causative agent. The late age at onset (mean 9 years), the very slow progression of clinical signs (mean 11 months) and the peculiar clinical presentation (particularly the posture of the tail) have not been reported previously in cats with lymphohistiocytic meningoencephalomyelitis.

 


 

 Friday, April 17, 2015

 

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay

 

>>> show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.

 


 


 

 

AD.63: Susceptibility of domestic cats to chronic wasting disease

 

Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1

 

1Colorado State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN USA

 

Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from these two cats were pooled and inoculated into cohorts of cats by IC, PO, and intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the symptomatic cats by western blotting and immunohistochemistry and abnormalities were seen in magnetic resonance imaging, including multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to- feline transmission in nature.

 


 

www.landesbioscience.com

 

PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)

 


 


 


 


 

PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)

 


 


 

Thursday, May 31, 2012

 

CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more

 


 

Monday, August 8, 2011

 

Susceptibility of Domestic Cats to CWD Infection

 


 

Sunday, August 25, 2013

 

Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

 


 

Feline Spongiform Encephalopathy (FSE) FSE was first identified in the UK in 1990. Most cases have been reported in the UK, where the epidemic has been consistent with that of the BSE epidemic. Some other countries (e.g. Norway, Liechtenstein and France) have also reported cases.

 

Most cases have been reported in domestic cats but there have also been cases in captive exotic cats (e.g. Cheetah, Lion, Asian leopard cat, Ocelot, Puma and Tiger). The disease is characterised by progressive nervous signs, including ataxia, hyper-reactivity and behavioural changes and is fatal.

 

The chemical and biological properties of the infectious agent are identical to those of the BSE and vCJD agents. These findings support the hypothesis that the FSE epidemic resulted from the consumption of food contaminated with the BSE agent.

 

The FSE epidemic has declined as a result of tight controls on the disposal of specified risk material and other animal by-products.

 

References: Leggett, M.M. et al.(1990) A spongiform encephalopathy in a cat. Veterinary Record. 127. 586-588

 

Synge, B.A. et al. (1991) Spongiform encephalopathy in a Scottish cat. Veterinary Record. 129. 320

 

Wyatt, J. M. et al. (1991) Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.

 

Gruffydd-Jones, T. J.et al.. (1991) Feline spongiform encephalopathy. J. Small Animal Practice. 33. 471-476.

 

Pearson, G. R. et al. (1992) Feline spongiform encephalopathy: fibril and PrP studies. Veterinary Record. 131. 307-310.

 

Willoughby, K. et al. (1992) Spongiform encephalopathy in a captive puma (Felis concolor). Veterinary Record. 131. 431-434.

 

Fraser, H. et al. (1994) Transmission of feline spongiform encephalopathy to mice. Veterinary Record 134. 449.

 

Bratberg, B. et al. (1995) Feline spongiform encephalopathy in a cat in Norway. Veterinary Record 136. 444

 

Baron, T. et al. (1997) Spongiform encephalopathy in an imported cheetah in France. Veterinary Record 141. 270-271

 

Zanusso, G et al. (1998) Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy. Lancet, V352, N9134, OCT 3, Pp 1116-1117.

 

Ryder, S.J. et al. (2001) Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy. Veterinary Record 146. 437-441

 

Kelly, D.F. et al. (2005) Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy. Veterinary Record 156. 472-477.

 


 

3 further cheetah cases have occured, plus 1 lion, plus all the primates, and 20 additional house cats. Nothing has been published on any of these UK cases either. One supposes the problem here with publishing is that many unpublished cases were _born_ long after the feed "ban". Caught between a rock and a hard place: leaky ban or horizontal transmission (or both).

 


 


 

YOU explained that imported crushed heads were extensively used in the petfood industry...

 


 

In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed...

 


 


 

on occassions, materials obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture...

 


 

*** Meldrum's notes on pet foods and materials used

 


 

*** BSE & Pedigree Petfoods ***

 


 

Tuesday, June 11, 2013

 

Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant deviations from requirements in FDA regulations that are intended to reduce the risk of bovine spongiform encephalopathy (BSE) within the United States

 


 

Wednesday, July 15, 2015

 

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?

 


 

 

SEE OUR GOVERNMENT COVER UP OF MAD COW DISEASE IN THE USA ;

 

 

Tuesday, August 4, 2015

 

*** FDA U.S. Measures to Protect Against BSE ***

 


 

 

Thursday, July 30, 2015

 

*** Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

 


 

 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 


 

 

*** Singeltary comment ;

 


 

 

 

Terry S. Singeltary Sr.

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