Press Release 07-048
Alzheimer's, Parkinson's, Type 2 Diabetes Similar at Molecular Level
Protein analysis may offer new therapeutic route
April 30, 2007
Alzheimer's disease, Parkinson's disease, type 2 diabetes, the human version
of mad cow disease, and other degenerative diseases are more closely related
at the molecular level than scientists realized, a team reports this week in
an advanced online publication of the journal Nature.
While still preliminary, the research, could help scientists develop tools
for diagnosing such diseases, and potentially for treating them through
"structure-based drug design," said David Eisenberg, a UCLA chemist and
molecular biologist who is part of the research team.
The researchers studied the harmful rope-like structures known as amyloid
fibrils--linked protein molecules that form in the brain. The fibrils
contain a stack of water-tight "molecular zippers."
"With each disease, a different protein transforms into amyloid fibrils, but
all of these diseases are similar at the molecular level," Eisenberg said.
If the molecular zipper is universal in amyloid fibrils, as Eisenberg
believes, is it possible to pry open the zipper or prevent its formation?
Eisenberg's research team used X-ray analysis and a sophisticated computer
algorithm to study proteins known to be associated with human diseases. When
the computer said a protein will form an amyloid fibril, it almost always
did. And one team member is experimenting with various compounds to break up
the fibrils.
"Structural analysis of micro-crystals of proteins is an example of how
basic research can have a profound impact on our understanding of health,
biotechnology and other practical issues," said Parag Chitnis, program
director in National Science Foundation's (NSF) Division of Molecular and
Cellular Biosciences.
NSF, the Howard Hughes Medical Institute and the National Institutes of
Health supported the research.
See the UCLA news release at
http://www.newsroom.ucla.edu/.
-NSF-
Media Contacts
Cheryl Dybas, NSF (703) 292-7734
cdybas@nsf.gov
Stuart Wolpert, UCLA (310) 206-0511
swolpert@support.ucla.edu
http://www.nsf.gov/news/news_summ.js...=NSF&from=news
TSS
----- Original Message -----
From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>
To: <BSE-L@aegee.org>
Sent: Wednesday, April 25, 2007 8:48 PM
Subject: TRANSMISSION OF B-amyloidosis TO PRIMATES strengthens the parallels
between Alzheimer's disease and CJD - IN CONFIDENCE
Subject: TRANSMISSION OF B-amyloidosis TO PRIMATES strengthens the parallels
between Alzheimer's disease and CJD - IN CONFIDENCE
Date: April 25, 2007 at 6:25 pm PST
IN CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
H F BAKER, R M RIDLEY, L W DUCHEN, T J CROW, C J BRUTON
As part of a larger series of experiments designed to assess the
transmissibility of various neurodegenerative disease including the
spongiform encephalopathies (eg Creutzfeldt-Jakob disease and BSE we
injected several marmosets (Callithrix Jacchus) intracerebrally with brain
homogenate from :
1) a 56 year old patient with severe Alzheimer's disease - B - amyloid
plaques and conogophilic angiopathy (CAA) and neurofibrillary tangles; and
2) a 62 year old patient with Gerstmann-Straussler disease, a spongiform
encephalopathy with PrP Plaques and, in this case, B-amyloid plaques and
CAA.
These monkeys were killed more than 6 years after inoculation and their
brains were found to contain moderate numbers of B-amyloid plaques and CAA
but NO neurofibrillary tangles NO PrP. The brains of more than 12 monkeys
killed at an older age did not contain these changes. B-amyloid was not
found in the brains of monkeys injected with brain material which did not
contain B-amyloid. These results suggest that B-amyloidosis is a
transmissible process resembling the transmissibility of PrP amyloidosis in
transmissible dementia and strengthens the parallels between Alzheimer's
disease and Creutzfeldt-Jakob disease.
It should be stressed, however, that we are not claiming to have transmitted
Alzheimer's disease because
1) the animals were behaving normally when killed and
2) no neurofibrillary tangles were seen.
We have argued previously that transmission of spongiform encephalopathy,
particularly from the genetic cases (GSS and some CJD), does not imply that
the donor cases themselves acquired the disease by infection. We would apply
the same arguments in this case, particularly in view of the genetic basis
of some cases of Alzheimer's disease and the extensive epidemiological data
which does not link Alzheimer's disease to infection.
DISCLOSURE
This work is currently under preparation for publication BUT IN VIEW OF
PUBLIC CONCERN OVER THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (eg BSE)
AND THE HIGH INCIDENCE OF ALZHEIMER'S DISEASE IN THE GENERAL POPULATION, IT
IS IMPORTANT THAT THESE FINDINGS ARE NOT DISCUSSED OPENLY BEFORE FULL
PUBLICATION.
Furthermore, BEFORE DISCLOSURE, IT IS IMPORTANT THAT INTERESTED PARTIES BE
PROPERLY APPRAISED OF THE DATA AND THERE IMPLICATIONS.
Previous attempts to transmit Alzheimer's disease to rodents and large
primates have been unsuccessful. It is our belief that post-mortem tissue
from these animals still exists and we are anxious that research workers (in
the USA) SHOULD NOT RE-EXAMINE this material until our data are published.
SAFETY
At this point we would like to stress again the lack of evidence relating
Alzheimer's disease to exposure to brain tissue through neurosurgery or
occupation. NEVERTHELESS it is appropriate that proper bodies should
consider whether the results of our experiments have any implications for
human health.
FURTHER EXPERIMENTS
The interpretation we have made that B-amyloidosis as a self-peretuating
process has important implications for understanding the process of
neurodegeneration, which are best studied at the level of protein chemistry.
However, we can see arguments for some transmission experiments including:
1) serial passage of B-amyloidosis in order to strengthen the evidence of
transmissibility;
2) transmission from other cases of Alzheimer's disease in order to
establish the generality of this effect;
3) transmission to primates which are allowed to run their full course, ie
to see whether the full syndrome of Alzheimer's disease develops including
neurofibrillary tangle formation, astrocytosis, neuronal loss and
concomitant cognitive decline. (We are already expert in the
neuropsychological assessment of marmosets). It should be remembered that,
at the present time, only the amyloidosis have been found to be
transmissible such that Alzheimer's disease PER SE has not been transmitted;
4) comparison of transmission from cases which contain only CAA and those
which contain only B-amyloid plaques. These two forms of amyloid differ very
slightly and it is not known whether this difference is preserved on
transmission;
5) establishment of the time course of the development of B-amyloidosis. The
present experiment suggests that the time course is somewhere between 1-5
years;
6) transmission using larger quantities of purified preparations of
B-amyloid. This may reduce the transmission time considerably;
7) transmission using animals of different initial ages to investigate the
relationship between transmission time and chronological age, eg
transmission into mature animals may decrease transmission time through an
interaction between the pathological process and senescence;
8) manipulation of transmission time by treatments which may speed up plaque
formation, eg by increasing the production of amyloid precursor protein, or
which may slow down plaque formation and protect from disease progression.
The proposal is to inoculate about 25 marmosets in the first instance and to
replace them in a 'rolling' experiment as they die or are killed according
to the experimental design. The marmosets will be kept in the MRC Marmoset
Colony in Cambridge. Additional facilities and personnel are not required
over and above that awarded to Dr. Ridley in an MRC Programma Grant.
A preliminary report of our findings will be presented by Professor L W
Duchan at the January 1993 meeting of the British Neuropathological Society.
http://www.bseinquiry.gov.uk/
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/y...1/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://www.bseinquiry.gov.uk/files/y...7/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a
molecular level...
snip...
http://www.bseinquiry.gov.uk/files/y...3/12003001.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/y...7/06005001.pdf
TSS