Non-infectious prion proteins found in the brain may contribute to Alzheimer's disease, researchers have found.
The surprising new results, reported this week in Nature1, show that normal prion proteins produced naturally in the brain interact with the amyloid-β peptides that are hallmarks of Alzheimer's disease. Blocking this interaction in preparations made from mouse brains halted some neurological defects caused by the accumulation of amyloid-β peptide. It was previously thought that only infectious prion proteins, rather than their normal, non-infectious counterparts, played a role in brain degeneration.
The results have yet to be confirmed in humans, but suggest that targeting the non-infectious prion protein (PrPc) could provide an alternative route to treating Alzheimer's disease. "The need is huge," says Paul Aisen, an Alzheimer's researcher based at the neurosciences department of the University of California, San Diego. "And it's great news for the field when a new idea is brought forth with strong evidence that can lead to new therapeutic strategies."
Proteins misbehaving
Alzheimer's disease has long been linked to the build-up of amyloid-β peptides, first into relatively short chains known as oligomers, and then eventually into the long, sticky fibrils that form plaques in the brain. The oligomeric form of the peptide is thought to be toxic, but exactly how it acts in the brain is unknown.
Stephen Strittmatter and his colleagues at Yale University in New Haven, Connecticut searched for brain cell proteins that interact with amyloid-β oligomers. To their surprise, they found PrPc, the normal, non-infectious prion protein.
Normal prion proteins are produced naturally in the brain, but can cause disease when they come into contact with an infectious form of the protein (PrPSc) that folds into an unusual conformation. These infectious prions convert innocuous prion proteins into the infectious form, which forms clumps and leads to neurodegenerative diseases, such as variant Creutzfeldt-Jakob disease, the human form of mad cow disease.
Strittmatter's team found that in brain slices taken from mice that were engineered to lack the prion protein, amyloid-β did not cause defects in a process called long-term potentiation, which is important for long-term memory formation. Similarly, using an antibody to block the prion protein also prevented damage caused by the errant amyloid-β peptides.
Therapeutic potential
Researchers have struggled to determine what prion proteins normally do in the brain. Mice that lack the protein appear largely normal, with possible minor deficits in the generation of new neurons and responses to stress. A recent study found evidence that the prion protein may also be necessary for mice to have a normal sense of smell2.
Nevertheless, the results in mice suggest that blocking the protein may have unwanted side-effects, says Lennart Mucke, a neurologist at the Gladstone Institute of Neurological Disease in San Francisco, California. Although some are already at work to develop drugs that target the prion protein, these programmes target the infectious form of the protein and may not be useful in warding off Alzheimer's disease.
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But Strittmatter and his colleagues mapped the region of the prion protein that interacts with amyloid-β, giving researchers a clear target in the search for inhibitors of this interaction. Mucke, meanwhile, points out that an enzyme called α-secretase can cleave the prion protein at a site that would prevent it from binding to amyloid-β. This same enzyme can also cleave amyloid-β itself, meaning that enhancing that enzyme's activity could yield two strikes against Alzheimer's disease.
Although more work needs to be done to confirm the results in animal and human studies, Aisen says Alzheimer's disease researchers will welcome a new target in the fight against the frustrating disease. Clinical trials are underway to test drugs that aim to reduce the levels of amyloid-β in the brain, but researchers are pessimistic about ever driving amyloid-β levels down to zero. Meanwhile, treatments already on the market target symptoms of the disease, and not it's underlying cause.
"The treatments we have for Alzheimer's disease today are symptomatic and entirely inadequate," says Aisen. "There's no question that we need treatments that target the mechanisms behind neurodegeneration in Alzheimer's disease."
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References
- et al. Nature 457, 1128- 1132 (2009).
- et al. Nature Neuroscience 12, 60- 69 (2008).
P03.139 Cellular Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer?s Amyloid Precursor Protein Hooper, NM1; Parkin, ET1; Watt, NT1; Baybutt, H2; Manson, J2; Hussain, I3; Turner, AJ1 1University of Leeds, Institute of Molecular and Cellular Biology, UK; 2Roslin Institute, Neuropathogenesis Unit, UK; 3GlaxoSmithKline, Neurodegeneration Research, UK Background: The normal cellular function of the prion protein (PrP), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease (CJD) in humans, remains enigmatic. Several studies have reported combinations of Alzheimer?s Disease (AD) and CJD neuropathology and the Val/Met129 polymorphism in the PrP gene has been identified as a risk factor for early-onset AD, leading to speculation that there may be some pathogenic connection between these two neurodegenerative conditions. The amyloid ß (Aß) peptides that cause AD are derived from the amyloid precursor protein (APP) through sequential proteolytic cleavage by the ß-secretase (BACE1) and the g-secretase complex. Aim: As both APP and PrP are cleaved by zinc metalloproteases of the ADAM family, we investigated whether PrP alters the proteolytic processing of APP. Results: Here we show that expression of PrP in SH-SY5Y cells dramatically downregulated the cleavage of APP by BACE1 and reduced the secretion of Aß peptides into the conditioned medium by >92%. Conversely, siRNA reduction of endogenous PrP in N2a cells led to an increase in secreted Aß. Furthermore, levels of Aß were significantly increased in the brains of PrP null mice as compared with wild type mice. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases, did not inhibit the BACE1 cleavage of APP. To investigate whether the Val/Met129 polymorphism in human PrPC would alter the production of Aß, brains from mice with the human PrP gene with MM or VV 129 genotypes were analysed. In the MM mice there was a significant increase in Aß in the brains as compared with the VV mice. In the brains of two strains (79A and 87V) of scrapie-infected mice there was a significant increase in Aß peptides as compared to uninfected mice. Conclusions: Together these data reveal a novel function for PrP in regulating the processing of APP through inhibition of BACE1. The increase in APP processing in cells expressing disease-associated forms of PrP and in scrapie-infected brains raises the possibility that the increase in Aß may contribute to the neurodegeneration observed in prion diseases. Funded by the Medical Research Council of Great Britain. P03.140 Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer?s Amyloid Precursor Protein through Interaction with Glycosaminoglycans Griffiths, HH; Parkin, ET; Watt, NT; Turner, AJ; Hooper, NM University of Leeds, Institute of Molecular and Cellular Biology, UK Background: Proteolytic processing of the amyloid precursor protein (APP) by ßsecretase, BACE1, is the initial step in the production of the amyloid ß (Aß) peptide which is involved in the pathogenesis of Alzheimer?s disease. We have shown that the cellular prion protein (PrP) inhibits the cleavage of APP by BACE1 in cell and animal models. Aim: To investigate the mechanism by which PrP inhibits the action of BACE1. Results: Neither PrPdeltaGPI, which is not membrane attached, nor PrP-CTM, which is anchored by a transmembrane domain and is excluded from cholesterol-rich lipid rafts, reduced cleavage of APP, suggesting that to inhibit the BACE1 cleavage of APP PrP has to be localised to lipid rafts. Coimmunoprecipitation experiments demonstrated that PrP physically interacts with BACE1. However, PrP did not alter the activity of BACE1 towards a fluorogenic peptide substrate nor perturb the dimerisation of BACE1. Using constructs of PrP lacking either the octapeptide repeats or the 4 residues KKRP at the N-terminus of the mature protein (PrPdeltaN), we demonstrate that the KKRP sequence but not the octapeptide repeats, is essential for regulating the BACE1 cleavage of APP. As the KKRP sequence is known to participate in glycosaminoglycan (GAG) binding, we confirmed that PrPdeltaN did not bind to immobilised heparin. Addition of heparin to SH-SY5Y cells increased the amount of APP cleaved by BACE1 in a concentration-dependent manner and reduced the amount of BACE1 coimmunoprecipitated with PrP, suggesting that GAGs are required for PrP to interact with BACE1 and inhibit APP processing. Of a range of GAGs, including dextran sulphate, hyaluronic acid and chondroitin sulphate, investigated there was complete correlation between those that could restore BACE1 cleavage of APP in PrP expressing cells and those that bound PrP. Conclusion: These data suggest a possible mechanism by which PrP regulates the ßcleavage of APP is through the N-terminus of PrP interacting via GAGs with one or more of the heparin binding sites on BACE1 within a subset of cholesterol-rich lipid rafts, thereby restricting access of BACE1 to APP. Funded by the Medical Research Council of Great Britain. P04.37 Comparison of the Neuropsychological Profile of Patients with Sporadic Creutzfeldt-Jakob Disease and Patients with Alzheimer?s Krzovska, M1; Cepek, L1; Ratzka, P2; Döhlinger, S3; Uttner, I1; Wolf, Stefanie4; Irle, Eva4; Mollenhauer, Brit5; Kretzschmar, Hans A.6; Riepe, Matthias7; v. Arnim, Christine1; Otto, Markus1 1University of Ulm, Germany; 2Department of Neurology, Germany; 3University of Goettingen, Germany; 4University of Goettingen, Germany; 5Elena Klinik, Germany; 6LMU, Germany; 7University of Berlin, Germany Background:To evaluate the neuropsychological profile of sCJD we administered the cognitive subscale of the Alzheimer?s Disease Assessment Scale (ADAS-cog) in order to determine if and how the sCJD-Subgroups (Met/Met, Met/Val, Val/Val) have different results in the item analysis of the ADAS-cog. Furthermore, we studied how the scores differ from that of patients with Alzheimer?s disease (AD). Methods:33 sCJD patients (11 with definite CJD and 22 with probable CJD) underwent neuropsychological testing with the ADAS-cog and Mini Mental State Exam (MMSE). Of these 31 were genotyped at the Codon 129 (11 Val/Val, 18 Met/Val and 2 Met/Met). The patients were matched in regards to sex and total ADAS-cog score with AD patients. The scores of the 11 ADAS-cog items were compared between the sCJD and the AD groups as well as between the sCJD-subgroups Met/Val and Val/Val and the AD group. Results:The ADAS-cog total score of the sCJD and AD groups was 22.6+/- 6.5, respectively. Regarding the single Item scores of the sCJD patient group and the AD patient group, there were statistically significant differences in the Items Constructional praxis, Word-finding difficulty in spontaneous speech and Spoken language ability. When comparing the sCJD subtypes with each other no statistically significant difference was found in the items. Conclusion: In the speech domain and constructional praxis there is indication of greater impairment in sCJD patients in general when compared with AD patients. A disturbance of the speech appears to be an important characteristic of the Met/Val and Val/Val subtypes of sCJD, and should therefore be the focus of special attention in future neuropsychological studies. http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.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 Saturday, May 17, 2008 Are cheetahs on the run from prion-like amyloidosis? http://betaamyloidcjd.blogspot.com/2008/05/are-cheetahs-on-run-from-prion-like.html 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 snip... Greetings, I have two comments ; >>>To control the incidence of AA amyloidosis and reduce the likelihood of the animal?s extinction, prevention of the transmission with excretion from cheetahs with amyloidosis should be considered along with reduction of precursor SAA levels.<<< considering AA amyloidosis in humans, should we consider this same risk factor for humans, i.e. 'extinction' and 'prevention of transmission with excretion' and Alzheimer's ? >>>In particular, systemic AA amyloidosis is regarded as an increasingly important cause of morbidity and mortality in captive cheetahs as prevalence increased from 20% in pre-1990 reported necropsies to an unusual 70% of necropsied cheetahs in 1995 (14).<<< hmmm, big increase, and key word here is 'CAPTIVE'. WHAT WERE THESE CHEETAHS FED ? i.e. dead stock downers maybe ? These cheetahs are reported elsewhere to have been fed cattle delicacies such as split spinal cords, whole necks, whole skulls, and split skulls from which the knacker had "removed" CNS material, as late as 1993. Switcheroo -- MAFF web site mysteries 19 Apr 99 webmaster correspondence with MAFF "help" desk The MAFF staff actually responds helpfully to substantative question about material on their Web site though delays occur. The webmaster wrote MAFFon 16 April 1999 thanking them for their 15 Apr 99 update on animals that have succumbed to confirmed TSE and asking for dates of death on unpublished cases in tigers, ocelots, pumas, and bison that are listed on their site. These animals died some years back but nothing has ever appeared. On 17 Apr 99, the webmaster wrote again about something very puzzling: an allusion to cheetahs on line 15 and 29 whereas no such line numbers existed on the web page. Evidently they were holding back a line-by-line database of animals that would be very useful to scientists and conservationists around the world.. Very ominiouly, the cheetah lines went up to 29 whereas they showed "only" 5 British cheetahs (at Marwell and Whipsnade) plus 4 exported cheetahs [not furnished but Fota, Pearle Coast, and Safari de Peugres x 2]. There is nothing special about cheetahs and BSE other than they have a shorter incubation time than some of the other felids. These cheetahs are reported elsewhere to have been fed cattle delicacies such as split spinal cords, whole necks, whole skulls, and split skulls from which the knacker had "removed" CNS material, as late as 1993. No cheetah has ever been autopsied that did not display clinical signs of TSE; 11 cheetahs died at Marwell alone in the mid-90's but apparently were incinerated without autopsy or freezing samples despite the zoo's track record. The response to my polite inquiry: none. Well, actually there was a response: the MAFF webmaster quietly deleted any mention of the database. The switheroo occured on Mon, Apr 19, 1999 10:59 AM GMT according to Netscape 'document info', taking the site back to an earlier version of the document not mentioning line 15 and 29 and deleting the name of Marwell Zoo (the cheetah BSE factory). However, I had saved the original page to disk. Here is what the deleted top secret MAFF page actually said: "Not included above are two cheetahs at zoos in Australia and the Republic of Ireland. Both were apparently litter mates and exported from Marwell zoo, where the cheetahs on lines 15 and 29 were born. Two cases in cheetahs were also confirmed in France, one in January 1997, in an animal born at Whipsnade zoo in 1989. Details are awaited for the second case, but it is reported to have been born in Britain*." *Why don't they just ring up the French team and find out -- they published the abstract 8 months ago in August of 1998. They gave a presentation at the Chester Zoo published in the Proceedings of the EAZWV on May 24-24, 1998. MAFF came through (somewhat) on 13 May 1999. Though the names of the zoos could not be supplied and the cheetah line 29 business could not be explained, birth and death dates of zoo BSE animals supplement the published record. http://www.mad-cow.org/zoo_cites_annotated.html New BSE-like disease found in cheetah 06/09/2007 - 17:52:28 A cheetah at a zoo in Nuremberg has died after contracting an illness similar to mad cow disease, becoming the first confirmed case in Germany of feline spongiform encephalopathy (FSE), city authorities said today. Lulu, a female cheetah born in 1998, had suffered for six weeks from problems that included trouble balancing and weakness in her hind legs, the Nuremberg city government said in a statement. The animal eventually was put to sleep, and tests by Bavarian and federal labs were positive for FSE, it added. It was unclear how and when Lulu became infected with the disease, which has a several-year incubation period, but Nuremberg authorities said it likely happened in the Netherlands, where she was born. Lulu moved to Germany at the age of 15 months, returned to the Netherlands five years later and arrived at the Nuremberg zoo in March 2006. http://www.breakingnews.ie/world/mhcwgbqlkfcw/ http://www.eveningecho.ie/news/bstory.asp?j=230658672&p=z3x659378&n=230659432 http://www.live-pr.com/en/bse-like-disease-detected-in-german-zoo-s-r1048136284.htm GREETINGS, interesting to say the least. how could this cheetah have contracted FSE? feed with FSE ? casual contact with FSE in zoo ? remember the man and his cat whom both had sporadic CJD; In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition. http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html: Image] Research letters Volume 352, Number 9134 [Image] 3 October1998[Previous] [Next] [Image][Image] Simultaneous occurrence of spongiform encephalopathy in a manand his cat in Italy [Image] Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, SergioFerrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, SalvatoreMonaco Transmissible spongiform encephalopathies (TSE) encompass inherited,acquired, and sporadic mammalian neurological disorders, and arecharacterised by the conversion of the cellular prion protein (PrP) in aninsoluble and protease-resistant isoform (PrPres). In human TSE, four typesof PrPres have been identified according to size and glycoform ratios, whichmay represent different prion strains. Type-1 and type-2 PrPres areassociated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 withiatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence thatvariant CJD is caused by the bovine spongiform encephalopathy (BSE)-prionstrain.2-4 The BSE strain has been identified in three cats with felinespongiform encephalopathy (FSE), a prion disease which appeared in 1990 inthe UK.5 We report the simultaneous occurrence of sporadic CJD in a man anda new variety of FSE in his cat. A 60-year-old man, with no unusual dietary habits, was admitted in November,1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, andmyoclonus. An electroencephalogram (EEG) showed diffuse theta-deltaactivity. A brain magnetic resonance imaging scan was unremarkable. 10 dayslater, he was speechless and able to follow only simple commands. RepeatEEGs showed periodic triphasic complexes. 2 weeks after admission, he wasmute, akinetic, and unable to swallow. He died in early January, 1994. His 7-year-old, neutered, female shorthaired cat presented in November,1993, with episodes of frenzy, twitching of its body, and hyperaesthesia.The cat was usually fed on canned food and slept on its owner's bed. Nobites from the cat were recalled. In the next few days, the cat becameataxic, with hindquarter locomotor dysfunction; the ataxia got worse andthere was diffuse myoclonus. The cat was killed in mid-January, 1994. No pathogenic mutations in the patient's PrP gene were found. The patientand the cat were methionine homozygous at codon 129. Histology of thepatient's brain showed neocortical and cerebellar neuronal loss,astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed apunctate pattern and paralleled spongiform changes (figure B). The cat'sbrain showed mild and focal spongiosis in deeper cortical layers of all fourlobes (figure C), vacuolated cortical neurons (figure D), and mildastrogliosis. The cerebellar cortex and the dentate nucleus were gliosed.Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, andcaudate nucleus (figure E). Western blot analysis of control and affectedhuman and cat brain homogenates showed 3 PrP bands of 27-35 kDa. Afterdigestion with proteinase K and deglycosylation, only samples from theaffected patient and cat showed type-1 PrPres, with PrP glycoform ratioscomparable to those observed in sporadic CJD1 (details available fromauthor). [Image] Microscopic sections of patient and cat brains A: Occipital cortex of the patient showing moderate spongiformdegeneration and neuronal loss (haematoxylin and eosin) and B: punctateperineuronal pattern of PrP immunoreactivity; peroxidaseimmunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortexshowing mild spongiform degeneration (haematoxylin and eosin).D:vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidaseimmunohistochemistry with antibody 3F4 shows punctate perineuronaldeposition of PrP in temporal cortex. This study shows a spatio-temporal association between human and felineprion diseases. The clinical features of the cat were different frompreviously reported cases of FSE which were characterised by gradual onsetof behavioural changes preceding locomotor dysfunction and ataxia.5Neuropathological changes were also at variance with the diffuse spongiosisand vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern ofPrP deposition, similar in the cat and in the patient, was atypical for aBSE-related condition. Evidence of a new type of FSE was further provided bythe detection of a type-1 PrPres, other than the BSE-associated type 4.2Taken together, our data suggest that the same agent strain of sporadic CJ involved in the patient and in his cat. It is unknown whether these TSE occurred as the result of horizontaltransmission in either direction, infection from an unknown common source,or the chance occurrence of two sporadic forms. 1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypicvariablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39:767-78 [PubMed]. 2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis ofprion strain variation and the aetiology of 'new variant' CJD. Nature 1996;383: 685-90 [PubMed]. 3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501[PubMed]. 4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJDand BSE. Nature 1997; 389: 448-50 [PubMed]. 5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiformencephalopathy: a review. Vet Annual 1993; 33: 1-10. ------------------------------------------------------------------------ Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e dellaVisione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy(S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto ZooprofilatticoSperimentale della Lombardia e dell' Emilia, Brescia =========================================TSS indeed there have been 4 documented cases of TSE in Lions to date. Lion 32 December 98 Born November 86 Lion 33 May 1999 (euthanased) Born November 81. Lion 36 Euthanased August 2000 Born July 87. Deteriorating hind limb ataxia. Lion 37 Euthanased November 2001 Male, 14 years. Deteriorating hind limb ataxia since September 2001. (Litter mate to Ref. 36.) http://www.defra.gov.uk/animalh/bse/index.html go to the url above, on the bar at the top, click on _statistics_, then in middle of next page, click on_other TSEs_. or go here; http://www.defra.gov.uk/animalh/bse/bse-statistics/level-3-tsestat.html: and http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html: http://www.bseinquiry.gov.uk/files/yb/1992/11/13001001.pdf: also; Reports on the clinical symptoms presented by these cats give a relatively homogeneous picture: Affected cats show a lack of coordination with an ataxia mainly of the hind limbs, they often fall and miss their target when jumping. Fear and increased aggressiveness against the owner and also other animals is often seen. They do not longer tolerate to be touched (stroked) and start hiding. These behavioural chances might be the result of a hypersensibility to touch and noise, but also to increased fear. Excessive salivation is another more frequently seen symptom. Cats with FSE in general show severe behavioural disturbances, restlessness and depression, and a lack of coat cleaning. Symptoms in large cats in general are comparable to those in domestic cats. A report on FSE (in german) has been presented in 2001 in the Swiss FVO Magazin. A paper on the first FSE case in a domestic cat in Switzerland is currently in press in the Journal Schweizer Archiv für Tierheilkunde (SAT). http://www.neurocenter-bern.ch/tse_e.shtml: Article Posted: 04/15/2007 9:16:48 PM Human and Animal Food Poisoning with Mad Cow a Slow Death an editorial by Terry S. Singeltary Sr. HUMAN AND ANIMAL FOOD POISONING WITH MAD COW DISEASEs A SLOW DEATH WITH all the pet food deaths mounting from tainted pet food, all the suffering not only the animals are going through, but there owners as well, why are owners of these precious animals not crying about the mad cow tainted animal carcasses they poison there animals with everyday, and have been for decades, why not an uproar about that? well, let me tell you why, they don't drop dead immediately, it's a slow death, they simply call it FELINE and or CANINE ALZHEIMER'S DISEASE, DEMENTIA OR MAD CAT/DOG DISEASE i.e. FSE and they refuse to document CSE i.e.Canine Spongiform Encephalopathy, but it's there and there is some strange pathological findings on that topic that was convientantly swept under the rug. Sadly, this happens everyday with humans, once again confidently swept under the rug as Alzheimer's and or dementia i.e. fast Alzheimer's. Who wants to spend money on an autopsy on an old dog or cat? Sadly, it's the same with humans, you get old and demented your either die or your family puts you in an old folks home and forgets about you, then you die, and again, no autopsy in most cases. Imagine 4.5 annually with Alzheimer's, with and estimated 20+ million dieing a slow death by 2050, and in reality it will most likely be much higher than that now that the blood supply has been infiltrated with the TSE agent, and we now know that blood is another route and source for this hideous disease. It's hell getting old now a days. NOW, for the ones that don't believe me, well mad cow has been in the USA for decades undetected officially, but the late Richard Marsh documented way back, again, swept under the rug. Then in 2003 in December, the first case of BSE was finally documented, by accident. Then you had the next two cases that were documented in Texas and Alabama, but it took an act of Congress, literally, to get those finally documented, and when they were finally documented, they were atypical BSE or Bovine Amyloid Spongiform Encephalopathy (BASE), which when transmitted to humans is not vCJD or nvCJD, but SPORADIC CJD. Now you might ask yourself what about that mad cow feed ban of August 4, 1997, the year my mother died from the Heidenhain Variant of Creutzfeldt Jakob Disease (confirmed), well that ruminant to ruminant was merely a regulation on paper that nobody enforced. Just last month there was 10+ PLUS MILLION POUNDS OF BANNED BLOOD TAINTED MBM DISPERSED INTO COMMERCE, and there is no way the FDA will ever recover it. It will be fed out again. 2006 was a banner year for FDA mad cow protein fed out into commerce. Looks like 2007 will be also. Our federal Government has failed us at every corner when it comes to food safety. maybe your dog, your cat, your mom, your dad, your aunt, or your uncle, but again, who cares, there old and demented, just put them down, or put them away. It's hell getting old. ...END http://www.swnebr.net/newspaper/cgi-bin/articles/articlearchiver.pl?160273 http://newhopetoday.blogspot.com/2007/04/article-posted-04152007-91648-pm-human.html http://www.emaxhealth.com/forums/showthread.php?t=12779 FELINE AND CANINE ALZHEIMER'S OR MAD CAT/DOG DISEASE AND PET FOOD ... ...TSS Name: Terry S. Singeltary Sr. Date: Jan 26, 2007 Dear Terry S. Singeltary Sr. ... specifically dry dog food, some of which was reported to have been ... [url]www.kxmb.com/getArticle.asp?ArticleId=113652[/url] - 107k - http://www.kxmb.com/getForumPost.asp?ArticleId=113652 FELINE AND CANINE ALZHEIMER'S OR MAD CAT/DOG DISEASE AND PET FOOD ... ...TSS Name: Terry S. Singeltary Sr. Date: Jan 26, 2007 Dear Terry S. Singeltary ... so that the dog food will not mistakenly be mixed into cattle or other ... [url]www.kxnet.com/t/schools/113652.asp[/url] - 107k - http://www.kxnet.com/getForumPost.asp?ArticleId=113652 Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer... http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.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 Human BSE snip... These are not relevant to any possible human hazard from BSE nor to the much more common dementia, Alzheimers. snip... http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf IN STRICT CONFIDENCE TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf see full text ; Alzheimer's and CJD http://betaamyloidcjd.blogspot.com/ Terry S. Singeltary Sr. P.O. Box 42 Baycliff, Texas USA 77518