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Alzheimer’s may 'seed' itself like mad cow disease

flounder

Well-known member
----- Original Message -----
From: "Terry S. Singeltary Sr." <[email protected]>
To: <[email protected]>
Sent: Thursday, September 21, 2006 1:52 PM
Subject: Alzheimer’s may 'seed' itself like mad cow disease


##################### Bovine Spongiform Encephalopathy
#####################


Subject: Alzheimer’s may 'seed' itself like mad cow disease
Date: September 21, 2006 at 11:46 am PST


Alzheimer’s may 'seed' itself like mad cow disease
19:00 21 September 2006
NewScientist.com news service
Roxanne Khamsi
Proteins taken from the brains of Alzheimer’s patients and injected into the
brains of genetically engineered mice trigger Alzheimer’s-like lesions in
the mouse brains, researchers report.
The findings suggest that the malformed protein clumps associated with
Alzheimer’s disease can “seed” themselves in a way reminiscent of the
missfolded proteins in prion diseases such as “mad cow” disease.

The exact causes of Alzheimer’s remain a mystery, but it appears that
beta-amyloid proteins contribute to the formation of disruptive plaques in
the brain. The neurological damage accumulates over years, causing loss of
memory, language and other crucial mental skills.

Experts studying how beta amyloid might promote plaque formation have
speculated that this might happen in a process similar to that in prion
diseases.

Infectious agents
Prion illnesses, such as mad cow disease, are special in that proteins
apparently act as the infectious agents, rather than genetic material or a
microorganism. In laboratory tests, animals that receive prion proteins
develop brain plaques and eventually die as a result.

Previous experiments have shown that injections of brain extracts from
Alzheimer’s patients can trigger brain plaque formation in marmoset monkeys
and mice.

But it has not been clear whether the beta-amyloid proteins themselves are
responsible for this effect, or some other component of the brain tissue,
says Lary Walker at Emory University in Atlanta, Georgia, US.

To investigate this, Walker's team used "APP23 mice" – genetically
engineered to carry the human gene with a mutation that causes the animals
to develop plaques in old age.

Seed hunting
When the young APP23 mice received brain extracts from either humans who had
died with Alzheimer’s disease, or from older APP23 mice, the young mice
developed brain plaques within weeks instead of the usual year.

Next, the team took brain extracts from old APP23 mice and exposed them to
molecules that specifically bind and disable beta-amyloid proteins. When
these treated extracts were injected into the brains of young mice, they did
not cause the formation of plaques.

“For the first time we show that the likely seed is beta amyloid itself,”
says Walker.

He notes that there is no evidence to suggest that beta amyloid alone can
accelerate Alzheimer’s-like plaques in mice that are not genetically
predisposed to the illness.

Walker adds that the evidence from the new experiment should encourage
scientists to find out which forms of beta amyloid might promote plaque
formation most aggressively in humans.

Journal reference: Science (DOI: 10.1126/science.1131864)


http://www.newscientist.com/article/dn10134-alzheimers-may-seed-itself-like-mad-cow-disease.html




Subject: Transmissibility of mouse AApoAII amyloid fibrils: inactivation by
physical and chemical methods
Date: March 22, 2006 at 6:31 am PST

The FASEB Journal Express Article doi:10.1096/fj.fj.05-4890fje
Published online March 20, 2006


Transmissibility of mouse AApoAII amyloid fibrils: inactivation by physical
and chemical methods

Huanyu Zhang, Jinko Sawashita, Xiaoying Fu, Tatsumi Korenaga, Jingmin Yan,
Masayuki Mori, and Keiichi Higuchi

E-mail contact: [email protected]


AApoAII amyloid fibrils have exhibited prion-like transmissibility in mouse
senile amyloidosis. We have demonstrated that AApoAII is extremely active
and can induce amyloidosis following doses less than 1 pg. We tested
physical and chemical methods to disrupt AApoAII fibrils in vitro as
determined by thioflavin T binding and electron microscopy (EM) as well as
inactivating the transmissibility of AApoAII fibrils in vivo. Complete
disruption of AApoAII fibrils was achieved by treatment with formic acid, 6
M guanidine hydrochloride, and autoclaving in an alkaline solution.
Injection of these disrupted AApoAII fibrils did not induce amyloidosis in
mice. Disaggregation with 6 M urea, autoclaving, and alkaline solution was
incomplete, and injection of these AApoAII fibrils induced mild amyloidosis.
Treatment with formalin, delipidation, freeze-thaw, and RNase did not have
any major effect. A distinct correlation was obtained between the amounts of
amyloid fibrils and the transmissibility of amyloid fibrils, thereby
indicating the essential role of fibril conformation for transmission of
amyloidosis. We also studied the inactivation of AApoAII fibrils by several
organic compounds in vitro and in vivo.

AApoAII amyloidosis provides a valuable system for studying factors that may
prevent transmission of amyloid disease as well as potential novel
therapies.


http://www.fasebj.org/cgi/content/abstract/fj.05-4890fjev1





another transmissible protein amyloidosis? what does this implicate with
Alzheimer's and TSE, if anything?.........TSS


CJD1/9 0185


Ref: 1M51A

IN STRICT CONFIDENCE


Dr McGovern From: Dr A Wight

Date: 5 January 1993

Copies: Dr Metters

Dr Skinner

Dr Pickles

Dr Morris

Mr Murray


TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES


1. CMO will wish to be aware that a meeting was held at DH yesterday,
4 January, to discuss the above findings. It was chaired by Professor
Murray (Chairman of the MRC Co-ordinating Committee on Research in
the Spongiform Encephalopathies in Man), and attended by relevant
experts in the fields of Neurology, Neuropathology, molecular biology,
amyloid biochemistry, and the spongiform encephalopathies, and by
representatives of the MRC and AFRC.

2. Briefly, the meeting agreed that:

i) Dr Ridley et als findings of experimental induction of p amyloid
in primates were valid, interesting and a significant advance in the
understanding of neurodegeneradve disorders;

ii) there were no immediate implications for the public health, and no
further safeguards were thought to be necessary at present; and

iii) additional research was desirable, both epidemiological and at the
molecular level. Possible avenues are being followed up by DH
and the MRC, but the details will require further discussion.

93/01.05/4.1


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





BSE101/1 0136


IN CONFIDENCE

5 NOV 1992

CMO From: Dr J S Metters DCMO 4 November 1992


TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES


1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have
recognised the public sensitivity of these findings and intend to report
them in their
proper context. This hopefully will avoid misunderstanding and possible
distortion by
the media to portray the results as having more greater significance than
the findings
so far justify.


2. Using a highly unusual route of transmission (intra-cerebral injection)
the
researchers have demonstrated the transmission of a pathological process
from two
cases one of severe Alzheimer's disease the other of Gerstmann-Straussler
disease to
marmosets. However they have not demonstrated the transmission of either
clinical
condition as the "animals were behaving normally when killed'. As the report
emphasises the unanswered question is whether the disease condition would
have
revealed itself if the marmosets had lived longer. They are planning funher
research
to sec if the conditions, as opposed to the partial pathological process, is
transmissible.


What are the implications for public health?


3. . The route of transmission is very specific and in the natural state of
things
highly unusual. However it could be argued that the results reveal a
potential risk,
in that brain tissue from these two patients has been shown to transmit a
pathological
process. Should therefore brain tissue from such cases be regarded as
potentially
infective? Pathologists, morticians, neuro surgeons and those assisting at
neuro
surgical procedures and others coming into contact with "raw" human brain
tissue
could in theory be at risk. However, on a priori grounds given the highly
specific
route of transmission in these experiments that risk must be negligible if
the usual
precautions for handling brain tissue are observed.


92/11.4/1-1


BSE101/1 0137


4. The other dimension to consider is the public reaction. To some extent
the GSS
case demonstrates little more than the transmission of BSE to a pig by
intra-cerebral
injection. If other prion diseases can be transmitted in this way it is
little surprise that
some pathological findings observed m GSS were also transmissible to a
marmoset.
But the transmission of features of Alzheimer's pathology is a different
matter, given
the much greater frequency of this disease and raises the unanswered
question whether
some cases are the result of a transmissible prion. The only tenable public
line will
be that "more research is required" before that hypothesis could be
evaluated. The
possibility on a transmissible prion remains open. In the meantime MRC needs
carefully to consider the range and sequence of studies needed to follow
through from
the preliminary observations in these two cases. Not a particularly
comfortable
message, but until we know more about the causation of Alzheimer's disease
the total
reassurance is not practical.


JS METTERS
Room 509
Richmond House
Pager No: 081-884 3344
Callsign: DOH 832

121/YdeS

92/11.4/1.2


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





ORIGINAL STUDY FROM SCIENCE TODAY



Exogenous Induction of Cerebral

b-Amyloidogenesis Is Governed

by Agent and Host



Melanie Meyer-Luehmann,1* Janaky Coomaraswamy,1* Tristan Bolmont,1,2*
Stephan Kaeser,1

Claudia Schaefer,1 Ellen Kilger,1 Anton Neuenschwander,3 Dorothee
Abramowski,3 Peter Frey,3

Anneliese L. Jaton,3 Jean-Marie Vigouret,3 Paolo Paganetti,3 Dominic M.
Walsh,4

Paul M. Mathews,5 Jorge Ghiso,6 Matthias Staufenbiel,3 Lary C. Walker,7†
Mathias Jucker1,2†

Protein aggregation is an established pathogenic mechanism in Alzheimer’s
disease, but little is

known about the initiation of this process in vivo. Intracerebral injection
of dilute, amyloid-b (Ab)–

containing brain extracts from humans with Alzheimer’s disease or b-amyloid
precursor protein

(APP) transgenic mice induced cerebral b-amyloidosis and associated
pathology in APP transgenic

mice in a time- and concentration-dependent manner. The seeding activity of
brain extracts was

reduced or abolished by Ab immunodepletion, protein denaturation, or by Ab
immunization of the

host. The phenotype of the exogenously induced amyloidosis depended on both
the host and the

source of the agent, suggesting the existence of polymorphic Ab strains with
varying biological

activities reminiscent of prion strains.



snip...



There is currently no evidence that bamyloidosis

(and in particular AD) is transmissible

in the same sense as are prion diseases,

which can be transmitted to wild-type hosts via

diverse routes of varying efficiency and involve

systemic cellular mechanisms of prion uptake

and distribution (7, 32). However, an understanding

of the mechanisms involved in the

instigation and propagation of abnormal Ab

assemblies in vivo could shed light on the

origins of idiopathic Alzheimer_s disease. .............END



http://www.sciencemag.org/cgi/content/abstract/313/5794/1781



tss



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Kathy

Well-known member
All this injection process proves, is that the process "itself" transfers an agent which is responsible for causing new proteins to be manufactured in an abnormal way.

Clin Neuropathol. 2006 Jul-Aug;25(4):163-71

A vicious circle: role of oxidative stress, intraneuronal Abeta and Cu in Alzheimer's disease.

Bayer TA, Schafer S, Breyhan H, Wirths O, Treiber C, Multhaup G.
Department of Neurobiology, Clinic of Psychiatry, University of the Saarland, Homburg, Germany. [email protected]

Recent evidence indicates that both intraneuronal Abeta and Cu are involved in the pathological processes in Alzheimer's disease (AD). This perspective shows a possible interrelation of these factors. AbetaPP, the precursor of Abeta which represents the main constituent of amyloid plaques, is involved in Cu homeostasis in mammals. In vitro observations and in vivo data obtained from AbetaPP mouse models provide strong evidence that AbetaPP and the resulting Abeta overproduction facilitate intracellular Cu to leave the cell. An increased Cu efflux seems to lead to Cu deficiency and, subsequently, reduced SOD-1 activity. The Cu-dependent SOD-1 activity is the main enzyme involved in detoxifying free radicals. Several reports have shown that oxidative stress is an invariable age-dependent feature in the brain of AD patients. Increased oxidative stress leads to an increase in intraneuronal Abeta accumulation, which has been shown to be the main trigger for neuronal loss in transgenic mouse models. Thus, we conclude that bioavailability of Cu is a crucial point for the pathogenesis of AD.

PMID: 16866297
 

Kathy

Well-known member
Lets see the studies where aluminum, lead, cadmium and other metals are injected into the brains of these special mice.
 
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