SAGE KE Bulletin Board
Hasta la vista, amyloid cascade hypothesis, OR will academic dishonesty yield Alzheimer's cure?
26 May 2003
Alexei R. Koudinov
Neuron, Cell Press
1100 Massachusetts Avenue,
Cambridge, MA 02138
cc: Nobel Foundation, Alzheimer�s neuroscientists worldwide
I do not agree with (rather the doubt) your commentary  statement (associated with featured Neuron article of May 22, 2003 entitled �Antibodies against b-amyloid slow cognitive decline in Alzheimer's disease�) that i) "the effects of antibody production are impressive� and that ii) �the findings presented are important in providing further evidence for the validity of the prevailing working hypothesis, the Amyloid Cascade Hypothesis�. The doubt is implied in the opinion of a top-level Alzheimer�s researcher David Holtzman , and editor-in-chief of the top-level American experimental biology FASEB Journal Vincent Marchesi .
Dr. Holtzman found that �the title and some of the conclusions of this
study are not yet justified� . He specifies
that �the plasma and CSF Ab levels are not interpretable
with the technique used here.� Dr. Marchesi is �concerned about the different
results that are reported for the ELISA tests and the authors' tissue amyloid
plaque assay� (TAPIR) . Dr. Marchesi asks:
�Can we rule out some nonspecific immunological reactions that cause improvement
independent of the ability of the antibodies to bind to Ab?�
No, we can not. Moreover, I did not find experimental evidence that TAPIR
assay detects specifically Ab, not some other
constituent of the amyloid plaque [2,5].
Many studies showed great number of proteins in amyloid plaques (while
amyloid beta deposition was reported in a number of human disorders including
cardio-vascular pathology and several other neurodegenerative diseases
). Therefore, biological effects of Ab
(that Hock et al.  as well as the Winblad
and Blum  are blindly ignoring )
may trigger some biochemical changes [8,9]
and cause �nonspecific immunological reactions� .
I would call Neuron article  and
associated commentary  a bias in favor of
the expired amyloid dogma-based Alzheimer�s therapy approach in case of
a confidence of the authors' conflict of interest. Zurich group article
acknowledgment claims that there is no conflict: �the authors declare that
they have no competing financial interests related to Elan/Wyeth-Ayerst.�
Prof. Dr. Roger Nitsch institutional web site ,
however, indicates that his research is funded by �AHP-Wyeth-Elan", a reasonable
situation for a researchers performing clinical study �to the pharmaceutical
companies ELAN and WEYTH multi-center vaccination trial of Alzheimer's
disease� . Dr. Nitsh also chaired the symposium
on Alzheimer�s disease on July 15, 1999 during the IBRO Congress 1999 in
Jerusalem . This symposium was �kindly supported
by Elan Pharmaceuticals, NeoTherapeutics, Parke Davis�, indicating a situation,
fitting the conflict of interests definition by BMJ ,
a major general medicine journal.
The above indicates that there is a conflict by a senior author of the Neuron article by Hock et al. . If so, what is the reason of the dishonesty and breaking the cardinal tenet of academic science to make such conflict public and let readers decide whether the article �speaks for the science or for the company�  ?
Neuron readers also must know about the conflict associated with the key reference of the article by Hock et. al. This is �The National Institute on Aging, and Reagan Institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer's disease� , a Neurobiol Aging publication that has important follow up competing financial interest disclosure in The Wall Street Journal article �Did ties to Alzheimer's test maker sway NIH report?�  and in the Boston Phoenix article �Science for sale: a Harvard researcher stands to profit from a product he "independently" reviewed for the National Institutes of Health� . It was also covered as Nature Medicine report .
The above is tightly linked with my earlier correspondence with Neuron requesting editorial investigation and disciplinary action to punish Dennis J. Selkoe, (a Harvard professor, recent member of the NIH National Advisory Council on Aging, Athena founder and Elan director [14,18,19]), apparent non disclosure of competing financial interests in prior Neuron publication, and while serving Neuron editorial board member . You should be in receipt of my letter emailed to you and Emilie Marcus  on August 19, 2002. Shortly thereafter I received a reply from Neuron senior scientist Stacie Weninger. Dr. Weninger wrote to me: �I wanted to thank you for bringing this matter to our attention. We take these issues seriously, and we will look into the matter further� . Since then Neuron did not come to any action [that I expected to be] commensurate with the pattern of Dr. Selkoe misconducting academic nondisclosure dishonesty . Moreover, February 2003 Neuron article by Sharon et al.  again hided D. Selkoe (a senior author) competing financial interest, disclosure that is required by the academic ethics and the uniform requirements of the manuscripts submitted to the biomedical journals .
For a non disclosure of a competing interest in April 18, 2003 Science
report on amyloid oligomers (a brand-new Alzheimer's disease culprit substituting
amyloid plaque in the pathogenesis scheme by the amyloid cascade proponents
) please see Ref.
Competing financial interests: I do not
have any competing financial interest. I aim free information dissemination
and an unbiased development of Alzheimer's neuroscience. I observe the
for Neuroscience Guidelines
for Responsible Conduct Regarding Scientific Communication.
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2. Hock C, et al. Report: Antibodies against ß-Amyloid Slow Cognitive Decline in Alzheimer's Disease Neuron. 38, 547-554 (22 May 2003) [ Abstract ].
5. Hock C, et al. Generation of antibodies specific for beta-amyloid by vaccination of patients with Alzheimer disease. Nat Med. 8, 1270-5 (2002). [ PubMed ].
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9. Koudinova NV, Kontush A, Berezov TT, Koudinov AR. Amyloid beta, neural lipids, cholesterol and Alzheimer's disease. Neurobiol Lipids. 1, 6 (2003) [ FullText ].
10. Prof. Dr. Roger Nitsch. Neuro Science Center Zurich - Research Groups. University of Zurich web site. Last time viewed: May 26, 2003 [ FullText ].
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14. Ready T. Science for Sale: A Harvard researcher stands to profit from a product he "independently" reviewed for the National Institutes of Health. The Boston Phoenix. (29 April 1999) [ FullText ].
15. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. Consensus recommendations for the post-mortem diagnosis of Alzheimer's disease. Neurobiol. Aging.18, S1-S2 (1997) [ PubMed ].
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20. Selkoe DJ. Biography. ISI HighlyCited.com. Last updated August 15, 2001 [ FullText ].
21. Stacie Weninger response on Alexei Koudinov letter of August 19, 2002 (27 August 2002) [ FullText ].
22. Introduction. Handling Misconduct. Office of research integrity web site [ FullText ].
23. Sharon U, et al. The formation of highly soluble oligomers of a-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron. 37, 583-95 (2003) [ PubMed ].
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26. Koudinov AR. Alzheimer's
amyloid beta oligomers versus lipoprotein Abeta. Science SAGE KE.
(May 1, 2003) [ FullText
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