Alzheimer
2/2/2010
The US EPA and waste industry are promoting the landspreading of sewage sludge containing infectious human and
animal prions on grazing lands, hay fields, and dairy pastures. This puts livestock and wildlife at risk of infection.
They ingest large quantities of dirt and top dressed sludge with their fodder, Prion infected Class A sludge is spread
in parks, playgrounds, home lawns, flower and vegetable gardens - putting humans, family pets, and children with their
undeveloped immune systems and hand-to-mouth "eat dirt" behavior at risk. University of Wisconsin prion
researchers, working with $100,000 EPA grant and a $5 million Dept. of Defense grant, have found that prions become
680 times more infectious in certain types of soil. And human prions are 100,000 more difficult to inactivate than
animal prions
Recently, researchers at UC Santa Cruz, and other scientists around the country, announced that Alzheimer's Disease
(AD) is a prion disease. "Prion" = proteinaceous infectious particle which causes TSEs (Transmissible spongiform
encephalopathies) in humans and animals including BSE (Mad Cow Disease), scrapie in sheep and goats, and Chronic
Wasting Disease in deer, elk and moose. Human prion diseases are AD and CJD (Creutzfeldt Jakob Disease,) and
other rarer maladies. Infectious prions have been found in muscle tissue including heart, saliva, blood, urine, feces
and many other human and animal body organs.
Alzheimer's rates are soaring as Babyboomers age - there are now over 5.3 million AD victims in US shedding infectious
prions in their blood, urine and feces, into public sewers. No sewage treatment process inactivates prions - they are
practically indestructible. The wastewater treatment process concentrates the infectious prions in the sewage sludge.
See article belows - prions are evolving and becoming more virulent - infected sewage sludge should be thermally
treated and used to produce clean energy -- not spread on agricultural land, parks and playgrounds, home gardens -
to infect more people and animals.
http://www.stanford.edu/group/pandegroup/folding/FoldingFAQ.pdf
Folding@Home is based at Stanford University and Stanford University Medical School and is funded by the National
Institutes of Health and the National Science Foundation
What are proteins and why do they "fold"? Proteins are biology's workhorses -- its "nanomachines." Before proteins can
carry out their biochemical function, they remarkably assemble themselves, or "fold." The process of protein folding,
while critical and fundamental to virtually all of biology, remains a mystery. Moreover, perhaps not surprisingly, when
proteins do not fold correctly (i.e. "misfold"), there can be serious effects, including many well known diseases, such as
Alzheimer's, Mad Cow (BSE), CJD, ALS, and Parkinson's disease.
"
What happens if proteins don't fold correctly? Diseases such as Alzheimer's disease, cystic fibrosis, BSE (Mad Cow
disease), an inherited form of emphysema, and even many cancers are believed to result from protein misfolding. When
proteins misfold, they can clump together ("aggregate"). These clumps can often gather in the brain, where they are
believed to cause the symptoms of Mad Cow or Alzheimer's disease. "
http://thedailybite.wordpress.com/2010/01/02/prion-mad-cow-research-breakthrough-prions-evolve-and-adapt-like-
viruses/
Prion (mad cow) research breakthrough: Prions evolve and adapt like viruses!
January 2, 2010 · Leave a Comment
Some astounding research about the mysterious infectious agent behind Mad Cow disease and other dread diseases
that infect the brain has just been published.
Contact: Keith McKeown
Scripps Research Institute
Scripps Florida scientists show ‘lifeless’ prions capable of evolutionary change and adaptation
Research may point to more effective therapeutic targets for deadly prion diseases
JUPITER, FL – Scientists from The Scripps Research Institute have determined for the first time that prions, bits of
infectious protein devoid of DNA or RNA that can cause fatal neurodegenerative disease, are capable of Darwinian
evolution.
The study from Scripps Florida in Jupiter shows that prions can develop large numbers of mutations at the protein level
and, through natural selection, these mutations can eventually bring about such evolutionary adaptations as drug
resistance, a phenomenon previously known to occur only in bacteria and viruses. These breakthrough findings also
suggest that the normal prion protein – which occurs naturally in human cells – may prove to be a more effective
therapeutic target than its abnormal toxic relation.
The study was published in the December 31, 2009 issue of the journal Science Express, an advance, online edition of
the prestigious journal Science.
“On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses,”
said Charles Weissmann, M.D., Ph.D., the head of Scripps Florida’s Department of Infectology, who led the study. “This
means that this pattern of Darwinian evolution appears to be universally active. In viruses, mutation is linked to changes
in nucleic acid sequence that leads to resistance. Now, this adaptability has moved one level down – to prions and
protein folding – and it’s clear that you do not need nucleic acid for the process of evolution.”
Infectious prions (short for proteinaceous infectious particles) are associated with some 20 different diseases in humans
and animals, including mad cow disease and a rare human form, Creutzfeldt-Jakob disease. All these diseases are
untreatable and eventually fatal. Prions, which are composed solely of protein, are classified by distinct strains,
originally characterized by their incubation time and the disease they cause. Prions have the ability to reproduce,
despite the fact that they contain no nucleic acid genome.
Mammalian cells normally produce cellular prion protein or PrPC. During infection, abnormal or misfolded protein –
known as PrPSc – converts the normal host prion protein into its toxic form by changing its conformation or shape. The
end-stage consists of large assemblies (polymers) of these misfolded proteins, which cause massive tissue and cell
damage.
“It was generally thought that once cellular prion protein was converted into the abnormal form, there was no further
change,” Weissmann said. “But there have been hints that something was happening. When you transmit prions from
sheep to mice, they become more virulent over time. Now we know that the abnormal prions replicate, and create
variants, perhaps at a low level initially. But once they are transferred to a new host, natural selection will eventually
choose the more virulent and aggressive variants.“……
More at link including evidence that prions can form ‘quasi-species’ just like viruses. These agents of terrible central
nervous system diseases are far more complex and perhaps dangerous than thought. Some information about the
initial underestimation of the danger of the prion disease BSE, (mad cow), located in the second half of this post.
---
Déjà vu time.
1990: Gummer enlists daughter in BSE fight
The government has again attempted to reassure the public that British beef is safe, despite growing fears over the
cattle disease, Bovine Spongiform Encephalopathy (BSE).
The Minister of Agriculture, John Gummer, even invited newspapers and camera crews to photograph him trying to feed
a beefburger to his four-year-old daughter, Cordelia, at an event in his Suffolk constituency.
Although his daughter refused the burger, he took a large bite himself, saying it was “absolutely delicious”.
“Beef can be eaten safely by everyone, both adults and children, including patients in hospital”
Chief Medical Officer Sir Donald Acheson
His reassurances were echoed by the government’s Chief Medical Officer, Sir Donald Acheson, in a formal statement to
underline his previous assertions that beef is safe to eat.
He said that after taking advice from leading scientific and medical experts, he had no hesitation in saying that “beef
can be eaten safely by everyone, both adults and children, including patients in hospital”.
Gummer and his experts were tragically wrong.
In Context
By 1992, three cows in every 1,000 in Britain had BSE.
John Gummer’s attention-grabbing photocall rebounded dramatically when, in 1996, the government was finally forced
to admit there was a link between BSE and the human form of the disease, new variant CJD.
The EU banned the export of British beef – a ban that was not completely lifted for ten years – and the cattle market
collapsed as selective culls were carried out of cattle most at risk.
The photocall became the single thing that is most remembered about John Gummer’s political career, and “doing a
Gummer” has now passed into parliamentary slang.
Sent: Friday, January 29, 2010 7:42 PM
Subject: alz PRIONS EVOLVE - NO DNA - NEW STUDY
http://centralidahoextension.blogspot.com/2010/01/study-finds-prions-evolve-despite.html
Tuesday, January 5, 2010
Study finds prions evolve despite lacking DNA
By John Fauber
Milwaukee Journal Sentinel
December 31, 2009
Though they are believed to be "lifeless," the infectious agents known as prions that cause a variety of fatal brain
diseases in people and animals, including chronic wasting disease in deer, are capable of evolving like living organisms,
according a new study.
The research, which has implications for eventual treatments for such diseases, is one of the first studies to suggest
that something that is devoid of DNA or other genetic material can evolve in a Darwinian manner.
"It is really a novel concept," said Mark Beilke, a professor of medicine and chief of infectious disease at the Medical
College of Wisconsin.
Beilke, who was not involved in the research, said teaching the prion theory even to medical students is difficult. The
new paper, which was published online Thursday in the journal Science Express*, adds another complicated twist to the
prion concept, said Beilke, who also practices at Froedtert Hospital and the Clement J. Zablocki Veterans Affairs
Medical Center.
[* Abstract:
http://www.sciencemag.org/cgi/content/abstract/science.1183218
]
Beilke said the new finding makes sense.
Prions are abnormal versions of proteins made in the brain. Though they are believed to contain no genetic material
they are able to replicate in the brain by causing normal prion protein to misfold. That misfolding can turn the normally
harmless prion protein into infectious prions that cause incurable, fatal brain disorders such as chronic wasting disease,
scrapie and mad cow disease in deer, sheep and cattle as well as Creutzfeldt-Jakob disease and variant mad cow
disease in people.
Full text:
http://www.jsonline.com/features/health/80427567.html
Posted by Chad Cheyney at 10:00 AM
Alzheimer's And CJD
Scientifically Linked
By Michael Greger
12-29-03
http://www.rense.com/general46/alz.html
WORKS CITED
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Times, 27 March 1996d: 12A.
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Berger, Joseph R., et al. "Creutzfeldt-Jakob Disease: A Ten-Year Experience." Neurology, 44 (1994): A260.
Bleifuss, Joel. "Killer Beef." In These Times, 31 May 1993: 12-15.
Boller, F., O. L. Lopez, and J. Moossy. "Diagnosis of Dementia." Neurology, 38 (1989): 76-79.
Boule, Margie. "Despite Anectdotal Evidence, Docs Say No Mad Cow Disease Here." Oregonian, 16 April 1996: C01.
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Brayne, C. "How Common are Cognitive Impairment and Dementia?" Dementia and Normal Aging, Canbridge: University
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Brown, Paul. "Central Nervous System Amyloidoses." Neurology, 39 (1989): 1103-1104.
Davanpour, Zoreth, et al. "Rate of Creutzfeldt-Jakob Disease in USA." Neurology, 43 (1993): A316.
Flannery, Mary. "Twelve - Fifteen 'Mad Cow' Victims a Year in Area." Philadelphia Daily News, 26 March 1996: 03.
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Katzman. Cold Spring Harbor Laboratory, 1983.
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Hager, Mary and Mark Hosenball. "'Mad Cow Disease' in the U.S.?" Newsweek, 8 April 1996:58-59.
Harrison, Paul J., and Gareth W. Roberts. "'Life, Jim, But Not as We Know It'? Transmissible Dementias and the Prion
Protein." British Journal of Psychiatry, 158 (1991): 457-70.
Holman, R. C., et al. "Edidemiology of Creutzfeldt-Jakob Disease in the United States, 1979-1990." Neuroepidemiology,
14 (1995): 174-181.
Hoyert, Donna L. "Vital and Health Statistics. Mortality Trends for Alzheimer's Disease, 1979-1991." Washington: U.S.
Dept. of Health and Human Services, 1996.
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Manuelidis, Elias E. "Presidential Address." Journal of Neuropathology and Experimental Neurology, 44 (1985): 1-17.
Manuelidis, Elias E. and Laura Manuelidis. "Suggested Links between Different Types of Dementias: Creutzfeldt-Jakob
Disease, Alzheimer Disease, and Retroviral CNS Infections." Alzheimer Disease and Associated Disorders, 2 (1989):
100-109.
McKhann, Guy., et al. "Clinical Diagnosis of Alzheimer's Disease." Neurology, 34 (1984): 939.
Prusiner, S. "Some Speculations about Prions, Amyloid, and Alzheimer's Disease." New England Journal of Medicine,
310 (1984): 661-663.
Perry, R.T., et al. "Human Prion Protein Gene: Two Different 24 BP Deletions in an Atypical Alzheimer's Disease
Family." American Journal of Medical Genetics, 60 (1995): 12-18.
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Teixeira, F., et al. "Clinico-Pathological Correlation in Dementias." Journal of Psychiatry and Neuroscience, 20 (1995):
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1995.
Van Duijn, C. M. "Epidemiology of the Dementia: Recent Developments and New Approaches." Neuroepidemiology, 60
(1996): 478-488.
Van Duijn, C. M. "Epidemiology of the Dementia: Recent Developments and New Approaches." Neuroepidemiology, 60
(1996): 478-488.
Wade, J. P. H., et al. "The Clinical Diagnosis of Alzheimer's Disease." Archives of Neurology, 44 (1987): 24-29.
Wlazelek, Ann. "Fatal Brain Disease Mystifies Experts." Morning Call, 23 September 1990a: B01.
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Rate." Morning Call, 27 September 1990b: B04.
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http://www.cyber-dyne.com/~tom/Alzheimer_cjd.html#and%20C
http://www.sociocide.com/forums/showthread.php?t=54993
Not only did Prusiner establish a protein-based mechanism for the disease, but two years later he also purified the
protein involved. Toxic prions were discovered to be an evil doppelganger of a naturally occurring protein, which
purpose is unknown, but thought to have a basis in the maintenance of memory and certain stem cells. The toxic
protein is misfolded and by nature of its poor shape induces similar proteins to bind and form insoluble clumps of
protein called amyloid-beta plaques in neural tissue. This could explain its apparent ability to reproduce without a set of
nucleic acid instructions and its long latency period.
Recent research has connected these plaques with a wide range of diseases, including the big one: Alzheimer’s
disease. Researchers Adriano Aguzzi and Stephen Strittmatter have published a study of the damaging effects of
smaller, semi-soluble plaques on neurons in mice. They showed that the prion proteins are necessary for the damaging
effects of the semi-soluble plaques. “Researchers removed the prion protein middleman from mice and examined brain
slices. When the team washed A-beta oligomers* over the brain slices, the oligomers no longer had an effect on cell
activity in the hippocampus.” In a similar study, other researchers got the same results using an antibody primed to
block the section of prion protein that binds to the A-beta oligiomer. Without the prion proteins the damaging effects of
the disease weren’t seen. “Blocking prion protein binding may be a new therapeutic target for Alzheimer’s disease. Get
rid of the prion protein middleman, or its ability to bind A-beta oligomers, and get rid of the disease, said Strittmatter. "
Home / News / March 28th, 2009; Vol.175 #7 / Article
Prions complicit in Alzheimer’s disease
Supposedly harmless version plays a role in neuron malfunction
By Laura Sanders
March 28th, 2009; Vol.175 #7 (p. 10)
Text Size
Prion protein, notorious for causing the brain-wasting mad cow and Creutzfeldt-Jakob diseases, may also be a
coconspirator in Alzheimer’s disease, a new study in mice suggests.
In mad cow and Creutzfeldt-Jakob diseases, misshapen prion proteins do the damage. But the new paper, appearing
February 26 in Nature, offers evidence that the harmless version of the prion protein assists the amyloid-beta protein
responsible for brain cell death in Alzheimer’s disease.
“It’s pretty sensational,” comments Adriano Aguzzi, a neuropathologist at the University of Zurich. “What’s tremendously
electrifying is that prion protein may be a genetic sensor for extremely toxic, small concentrations of A-beta.”
A-beta proteins can travel alone or in groups in the brain. On their own, A-beta proteins are harmless. Massive,
insoluble clumps of A-beta, known as plaques, are probably harmless, too, says study coauthor Stephen Strittmatter, a
neuroscientist at Yale University. These plaques may be a gravestone marker of dead brain cells but are probably not
the killer. Instead, smaller, soluble clumps of 50 to 100 A-beta proteins, known as oligomers, are the most likely suspect,
Strittmatter says.
Earlier studies have shown that mice with A-beta oligomers can’t remember how to get through a maze as quickly as
mice without A-beta oligomers. Such oligomers prevent cross-talk between certain brain cells in the hippocampus of
mice, which helps explain the loss of learning and memory functions in Alzheimer’s disease.
But how these A-beta oligomers cause cellular mayhem is a mystery. The oligomers are toxic to cells at very low
concentrations, so it’s likely that specific proteins are exquisitely tuned to recognize the A-beta proteins. “What’s been
unclear is if A-beta acts on cells directly or if it acts through cell surface receptors, where it maybe corrupts the cell in
some way,” comments Lennart Mucke, a neuroscientist from the Gladstone Institute of Neurological Disease in San
Francisco and the University of California, San Francisco, who wrote a commentary in the same Nature issue.
Strittmatter and his colleagues searched for proteins embedded in the outer membrane of cells that might sense the
dangerous amyloid-beta oligomers. After screening 225,000 possible mouse proteins, only one specifically grabbed on
to the human form of A-beta: the prion protein. The protein bound to oligomers but not to single A-beta proteins.
The role of harmless prion protein, which is prevalent in the brain and peripheral tissues of healthy people and animals,
has been a mystery. “Everybody and his brother have been trying to find the normal function of prion protein,” Aguzzi
says.
Earlier reports suggest that the protein may help maintain the brain’s white matter and brain cell formation, and may
have a role in sensing smells. Even so, Aguzzi says, the matter is far from settled. “I never had the feeling that we’ve
come to the bottom of [prion protein’s] function,” Aguzzi says. But prion protein’s new job as an A-beta oligomer sensor
may shed light on how A-beta proteins can damage brain cells.
In the new study, researchers removed the prion protein middleman from mice and examined brain slices. When the
team washed A-beta oligomers over the brain slices, the oligomers no longer had an effect on cell activity in the
hippocampus. The researchers got the same results when an antibody blocked the 11 amino acids of prion protein
required for A-beta binding: no harmful A-beta effects. These “striking” results make the case that prion proteins are
crucial for A-beta–induced damage, Mucke says.
Blocking prion protein binding may be a new therapeutic target for Alzheimer’s disease. Get rid of the prion protein
middleman, or its ability to bind A-beta oligomers, and get rid of the disease. “In many ways it may be better than
addressing A-beta levels,” which are difficult to reduce completely, Strittmatter says.
The research is in very early stages. “Every new discovery raises more questions than it answers,” Mucke says, and
these findings are no exception. Researchers don’t yet know if prion protein and A-beta interact similarly in human
Alzheimer’s disease, or if blocking the connection between prion protein and A-beta is effective or safe in humans.
“How A-beta makes neurons sick was a black box,” Strittmatter says. “This research helps us understand the first step
of the process.”
http://emedicine.medscape.com/article/1168941-overview
eMedicine Specialties > Neurology > Neurological Infections
Prion-Related Diseases
Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine,
Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical
University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Coauthor(s): Arun Ramachandran, State University of New York Upstate Medical University
Contributor Information and Disclosures
Updated: Sep 21, 2009
Gerstmann-Strãussler-Scheinker disease, as described in a large kindred in 1936.52
Patients with this illness present with a slowly progressive limb and truncal ataxia, as well as dementia.
Death occurs 3-8 years following presentation.
The prominent involvement of the brainstem often leads to symptoms suggestive of olivopontocerebellar degeneration.
The pattern of inheritance is autosomal dominant and is caused by mutations of the PrP gene. The neuropathology of
GSS is remarkable in that extensive and invariable amyloid deposition occurs, in addition to the typical spongiform
change, gliosis, and neuronal loss. Interestingly, in several kindreds of GSS, extensive neurofibrillary tangle (NFT)
formation is found.53 NFTs are an essential feature of Alzheimer disease, but are also observed in other
neurodegenerative conditions.
Another variation of autosomal dominantly inherited human prionosis has been termed prion protein congophilic
angiopathy (ie, prion protein cerebral amyloid angiopathy [PrP-CAA]), which is characterized by cerebral vessel amyloid
deposition and the presence of NFT.54 Cerebral amyloid angiopathy (CAA) is also an essential feature of Alzheimer
disease. Both these variants of prionoses further link the pathogenesis of Alzheimer disease and the prion-related
diseases.
***********************************
http://ajp.amjpathol.org/cgi/content/abstract/174/4/1241
The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer’s Disease Hippocampus
Jeroen J.M. Hoozemans*, Elise S. van Haastert*, Diana A.T. Nijholt, Annemieke J.M. Rozemuller*, Piet
Eikelenboom and Wiep Scheper
From the Departments of Pathology,* and Psychiatry, Vrije Universiteit University Medical Center, Amsterdam; and the
Neurogenetics Laboratory, and Department of Neurology, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands
"Accumulation of misfolded proteins in the endoplasmic reticulum triggers a cellular stress response called the unfolded
protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins. Previously, we reported
that UPR activation is increased in Alzheimer’s disease (AD) patients. How the UPR relates to the pathological hallmarks
of AD is still elusive. In the present study, the involvement of UPR activation in neurofibrillary degeneration in AD was
investigated."
" A strong co-occurrence of immunoreactivity for both pPERK and glycogen synthase kinase 3β in neurons was also
observed. Together, these data indicate that UPR activation in AD neurons occurs at an early stage of neurofibrillary
degeneration and suggest that the prolonged activation of the UPR is involved in both tau phosphorylation and
neurodegeneration in AD pathogenesis. "
http://classes.uleth.ca/200301/chem2200a/glia.pdf
Neuroinflammation in Alzheimer’s
Disease and Prion Disease
P. EIKELENBOOM,1,2* C. BATE,3 W.A. VAN GOOL,2 J.J.M. HOOZEMANS,4
J.M. ROZEMULLER,5 R. VEERHUIS,4 AND A. WILLIAMS3
1Department of Psychiatry, Graduate School of Neurosciences, Vrije Universiteit Medical Center,
Amsterdam, The Netherlands
"ABSTRACT Alzheimer’s disease (AD) and prion disease are characterized neuropathologicallyby extracellular deposits
of AB and PrP amyloid fibrils, respectively. Iboth disorders, these cerebral amyloid deposits are co-localized with a
broad variety ofinflammation-related proteins (complement factors, acute-phase protein, pro-inflammatory cytokines)
and clusters of activated microglia. The present data suggest that the cerebral AB and PrP deposits are closely
associated with a locally induced, non-immunemediated chronic inflammatory response. Epidemiological studies
indicate that polymorphisms of certain cytokines and acute-phase proteins, which are associated with A plaques, are
genetic risk factors for AD. "
We also discuss the concept that the demonstration of a chronic inflammatorylike
process relatively early in the pathological cascade of both diseases suggests potential therapeutic strategies to
prevent or to retard these chronic neurodegenerative disorders. GLIA 40:232–239, 2002. © 2002 Wiley-Liss, Inc."
********************************************
http://www.physorg.com/news183706009.html
Flash frozen under the electron microscope: Examining the mechanical properties of Alzheimer’s amyloid fibrils
January 26, 2010
(PhysOrg.com) -- Alzheimer’s disease, Parkinson’s disease, type-II diabetes, and prion diseases like BSE all involve the
deposition of amyloid fibrils in tissues and organs. These are fibrous clumps of incorrectly folded proteins; their exact
structures and their roles in pathological processes are not yet completely understood.
Ads by Google
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By using electron microscopic images of flash frozen samples, researchers have now been able to examine the exact
structure of Alzheimer’s amyloid fibrils and to assess their mechanical properties. As the team reports in the journal
Angewandte Chemie, the fibrils are very stiff -- one of the underlying causes of their pathogenicity.
Because amyloid fibrils are very difficult to analyze with traditional biophysical techniques, Marcus Fändrich (Max Planck
Unit for Enzymology of Protein Folding, Halle/Saale, Germany), Carsten Sachse (MRC Laboratory of Molecular Biology,
Cambridge, UK), and Nikolaus Grigorieff (Brandeis University, Waltham, USA) were forced to take another approach:
They examined Alzheimer’s amyloid fibrils by electron cryomicroscopy. “These experiments allowed us to examine the
structure of the fibrils at a previously unattainable resolution,” explains Fändrich.
The fibrils appear in twisted bands about 20 nm wide and are often bent in the raw electron microscopic images. “These
bent fibrils are a snapshot of the fibrils in solution,” says Fändrich. “We use the degree of bending and twisting to
calculate how stiff the fibrils are.” This revealed that the Alzheimer’s amyloid fibrils are relatively rigid structures. “The
uncontrolled formation of such stiff fibrils is presumably critical for the pathogenicity of amyloid fibrils,” reports Fändrich.
“In many amyloid diseases, the fibrils are preferentially deposited in tissues that are normally contractile or elastic, like
the heart muscle or the walls of blood vessels. Medical findings indicate that the fibrils somewhat stiffen these tissues.”
“In addition, our data may help to better evaluate the possible uses of amyloid fibers as novel biotechnological agents,”
reports Fändrich. Based on their material properties and ease of modification, amyloid fibers are potentially interesting
as novel building materials.
More information: Marcus Fändrich, Nanoscale Flexibility Parameters of Alzheimer Amyloid Fibrils Determined by
Electron Cryo-Microscopy, Angewandte Chemie International Edition 2010, 49, No. 7, Permalink: http://dx.doi.org/10.
1002/anie.200904781
Provided by Wiley (news : web)
February 2009
http://science-education.nih.gov/home2.nsf/feature/index.htm
NATIONAL INSTITUTES OF HEALTH – OFFICE OF SCIENCE EDUCATION
Prions: Puzzling Infectious Proteins
Ruth Levy Guyer, Ph.D.
Sometimes a scientific discovery shakes the confidence of scientists, making them question whether they truly
understand nature's "ground rules."
That's exactly what prions have done to scientists' understanding of the ground rules for infectious diseases. Prions
cause diseases, but they aren't viruses or bacteria or fungi or parasites. They are simply proteins, and proteins were
never thought to be infectious on their own. Organisms are infectious, proteins are not. Or, at least, they never used to
be.
Prions entered the public's consciousness during the mad cow epidemic that hit England in 1986. For decades,
however, scientists had searched for unusual, atypical infectious agents that they suspected caused some puzzling
diseases that could not be linked to any of the "regular" infectious organisms. One possibility was that slow viruses--
viruses that spent decades wreaking havoc in their hosts--might be the culprits, and these putative viruses were not
only leisurely about multiplying but also hard to isolate. Now researchers are coming around, albeit reluctantly, to
accepting the shocking fact that naked proteins can be infectious. "More than one protein chemist has declared this to
be insane--and yet this is precisely what is implied by a growing number of studies" was the way one news article put it
(1).
Prions (pronounced pree-ahns) enter cells and apparently convert normal proteins found within the cells into prions just
like themselves. The normal cell proteins have all the same "parts" as the prions--specifically the same amino acid
building blocks--but they fold differently. They are much like the toy "Transformers" that intrigued little kids in the 1980s.
A sphynx could become a robot; a bug could become a warrior. Nothing was added; nothing subtracted.

Prions enter brain cells and there convert the normal cell protein PrPC to the prion form of the protein, called PrPSC.
When normal cell proteins transform into prions, amino acids that are folded tightly into alpha helical structures relax
into looser beta sheets. More and more PrPC molecules transform into PrPSC molecules, until eventually prions
completely clog the infected brain cells. The cells misfire, work poorly, or don't work at all. In mad cow disease, for
example, with their brain cells running amuck, the mad cows wobble and stagger and appear fearful--their "madness" is
craziness, not anger. Sheep and goats with the disease scrapie, which is like mad cow disease, become so
uncomfortable and itchy that they frantically rub up against anything they can, finally scraping off--hence, the name of
the disease--most of their wool and hair (2).

Proteins consist of stretches of amino acids (A). Some fold into alpha helices; others fold into beta pleated sheets (B).
These shapes are maintained by hydrogen bonds (indicated by dots). The sheets and helices then fold together further
to form the protein's tertiary structure (C). A protein, such as the one illustrated here, can include both alpha helices
and beta sheets and can consist of several subunits that combine to form the quaternary structure (D). When PrPC
molecules transform into PrPSC molecules, sections of the protein that were folded as alpha helices open out into beta
sheets. This illustration of the levels of protein structure is taken from BIOLOGY: CONCEPTS & CONNECTIONS by Neil
A. Campbell, Lawrence G. Mitchell, and Jane B. Reece. Copyright 1994 by The Benjamin/Cummings Publishing
Company, Inc. Reproduced by permission.
Ultimately, infected prion-bloated brain cells die and release prions into the tissue. These prions then enter, infect, and
destroy other brain cells (2). And, as clusters of cells die, the brain stops looking like a brain and starts looking more
like Swiss cheese. The medical term for the prion diseases is "spongiform encephalopathies," in acknowledgement that
the sick brains (encephalo is Greek for brain; pathy is Greek for disease) are riddled with holes and have taken the
form of sponges.

Shepherds and farmers whose sheep had scrapie never seemed to get scrapie themselves. So, for a long time,
scientists assumed that the prions of animals did not cause infections in humans. But, between 1994 and 1996, 12
people in England came down with Creutzfeld-Jakob disease (CJD), a human prion disease whose symptoms are not
unlike those of the mad cows, and all the victims had eaten beef from cows suspected of having mad cow disease. In
October, 1996, scientists in England reported that the prions from ten of the British patients were remarkably like those
of the mad cows and not like those of people who died of "classical" CJD (3). Scientists quickly realized that the
occurrence of CJD in a dozen people 19 to 39 years old was cause for alarm, because CJD had always been rare--
typically one new case might be diagnosed per million people each year--and seldom occurred in people younger than
55 (1, 3). This epidemic was something new, something extraordinary. Scientists now speculate that the prions that
started out in sheep suffering from scrapie made their way into cows and then moved more recently into humans. Cattle
are fed meal made from sheep "offal," the bones and other waste parts of sheep carcasses. Standard procedures for
grinding up carcasses were altered in the 1970s, and the new processing methods seem not to have been adequate for
destroying scrapie prions. The cattle were exposed, through the offal, to sheep prions, and the prions eventually
established themselves in their cow hosts. Later, they adapted further, infecting cells of people who had eaten
hamburgers from prion-bearing cows.

Scrapie is an old disease, recognized in sheep and goats for more than 250 years. In 1982, it was first identified as a
prion disease. The word "prion" was coined at that time by Dr. Stanley Prusiner to indicate that this disease was caused
by a "proteinaceous infectious agent." The protein that causes this and all other prion diseases is called PrPSC, which
stands for prion protein of scrapie (2).
At the moment, CJD and only a handful of other human diseases have clear links to prions. But it is likely that prions will
turn out to be the agents of a variety of currently enigmatic diseases in which brain cells are destroyed and the nervous
system deteriorates. Alzheimer's disease and Parkinson's disease are two prime candidates.
So, a couple new ground rules now seem to govern infectious diseases. The first is that naked proteins--prions--can be
infectious and can cause infectious diseases. The second and potentially more troubling is that, like other infectious
agents, prions can jump species' barriers and cause deadly diseases in humans. Recently, and for the first time known,
two farmers with mad cows in their herds died of CJD.
http://www.nature.com/nrmicro/journal/v4/n3/execsumm/nrmicro1346.html
Review
Nature Reviews Microbiology 4, 201–211 (1 March 2006) | doi:10.1038/nrmicro1346
Prions and their lethal journey to the brain
Prion diseases are neurodegenerative conditions that cause extensive damage to nerve Neil A. Mabbott & G. Gordon
MacPherson
Abstract
cells within the brain and can be fatal. Some prion disease agents accumulate first in lymphoid tissues, as they make
their journey from the site of infection, such as the gut, to the brain. Studies in mouse models have shown that this
accumulation is obligatory for the efficient delivery of prions to the brain. Indeed, if the accumulation of prions in
lymphoid tissues is blocked, disease susceptibility is reduced. Therefore, the identification of the cells and molecules
that are involved in the delivery of prions to the brain might identify targets for therapeutic intervention. This review
describes the current understanding of the mechanisms involved in the delivery of prions to the brain.
http://eon.businesswire.com/portal/site/eon/permalink/?ndmViewId=news_view&newsId=20100211006100&newsLang=en
OPKO Health Announces Development of Blood Test for Alzheimer’s Disease
February 11, 2010 10:47 AM Eastern Time
MIAMI--(EON: Enhanced Online News)--OPKO Health, Inc. (NYSE Amex:OPK) today announced the development of a
simple diagnostic blood test for Alzheimer’s disease. The test, designed to detect elevated levels of antibodies unique
to Alzheimer’s disease, was approximately 95% accurate in initial testing.
“OPKO has begun to develop a range of new diagnostic tests for other neurological diseases, as well as cancers,
starting with those for which early diagnosis is particularly important.”
The novel Alzheimer’s disease-specific antibodies were discovered using a proprietary platform being developed by
OPKO that appears to be capable of identifying such biomarkers for any disease to which the immune system reacts,
including cancer, autoimmune disease, neurodegenerative and infectious diseases. OPKO will perform additional
studies required for regulatory approval and commercial use. The test could be useful in identifying patients for clinical
trials for new Alzheimer’s drugs as well as to confirm the diagnosis in a clinical setting.
Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO, stated, “OPKO has begun to develop a range of
new diagnostic tests for other neurological diseases, as well as cancers, starting with those for which early diagnosis is
particularly important.”