Drs. Koudinov
Clin Med Health Res 2001 article gateway
"Brain Cholesterol Pathology is the Cause of Alzheimer's Disease"

Holy Land, November 27, 2001
Dear Colleagues,

The article that we hope you will like has dual structure. First, it is  a sounding board, a commentary or a teaching essay. It provides our viewpoint on Alzheimer's pathogenesis and represents our new, i.e. not reported previously, interpretation of previously published data. As such this contribution was presented as teaching poster and press book lay language article at the Society for Neuroscience Annual Meeting 2001 in San Diego, CA, November 11-15, 2001.

The novelty of our interpretation of the role of cholesterol in Alzheimer's disease was first encouraged in December 2000 when The Lancet welcomed us to submit a hypothesis manuscript. The later version of the Lancet hypothesis under our commentary/viewpoint definition was submitted to Nature Medicine, Trends in Neurosciences, Proceedings of the National Academy of Sciences USA, Neuron, New England Journal of Medicine, Nature Cell Biology and Nature Review Neurosciences. Lately, based on one reviewer comment, the manuscript was rejected from Archives of Neurology where it was submitted by invitation. During the presubmission inquiry with The British Medical Journal (BMJ) editorial staff kindly suggested us to publish this article in Clin Med Health Res. To adapt the article for Clin Med  we enhanced it with original data. These data (representing another article part) awaited publication but were reported last year as scientific session and lay language press book article at the Society for Neuroscience Annual meeting 2000, November 5, 2000, New Orleans, LA.

Please note that top biomedical journals found the article interesting but refused to accomodate it on their pages. "We certainly like to publish articles that, as yours, aim to present a novel and alternative view on a given topic" - wrote to us editor of one premier neuroscience journal, but added that he is "hesitant to publish ...non-mainstream article on the topic until we have covered the current trends on Alzheimer's research." Another very high impact medical journal wrote about the manuscript in the rejection letter dated August 1, 2001: "We thought that it was interesting, but that its focus, content, and interest to our readers were such that it would not meet our needs." 

Well. Thanks to technology and wonderful BMJ.COM venture we have an opportunity to take responsibility in presenting here our own Alzheimer's trend and let you decide yourself whether this article is interesting and important or not. If you like or dislike the article or would like to add few responsible words, please do so, at the exclusive ClinMed web site. Please don't be hesitant. Be sure that your post-publication peer review or commentary response will be published and will significantly contribute to the discussion on the role of cholesterol in neurodegeneration, brain function, synaptic plasticity, tau and amyloid beta neurochemistry and Alzheimer's disease. The BMJ commitment to provide free and unlimited discussion forum through eResponses on any article that appear in BMJ  journals reserves the trust and was verified by us previously.

We believe that we did a good job to deliver to you professionally looking web html-enhanced and Acrobat .PDF article versions. We hope that you will enjoy reading the article and will find it helpful in your scientific endeavors.

With best regards from the Holy Land,

Alexei R. Koudinov, MD, PhD

Natalia V. Koudinova, MD, PhD

Post Scriptum
December 18, 2001 note: We are happy to let you know that HTML version of the paper had 500 readers during first three weeks since it was published on November 27, 2001


Brain Cholesterol Pathology is the Cause of Alzheimer's Disease.
Koudinov AR, Koudinova NV
Clin Med Health Res (2001) Published online November 27, 2001. clinmed/2001100005

[ Current article Hit Parade: 2356 readers ]

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HTML version of the article aims to become your desktop reference center. It has 71 references, 13 WEB+ and 11 supplementary web-only references and provides instant access to the citations abstracts and full text.

Lay language summary for this article is also available in the format of The Society for Neuroscience 2001 Press book article.


Several recent reports provided important knowledge on how “inhibiting cholesterol production in the brain might inhibit amyloid b(Ab) production, and reduce the accumulation of Ab that causes Alzheimers disease (AD)”. As we show and discuss here cholesterol homeostasis biological misregulation itself has a key role for synaptic plasticity impairment, neuronal degeneration and is the primary cause for several AD hallmarks not limited to brain amyloid. Moreover, Alzheimer's changes in neurochemistry of Ab, tau, neuronal cytoskeleton, and oxidative stress reactions likely represent physiological transitory mechanisms aiming to compensate impaired brain cholesterol dynamics and/or associated neurotransmission and synaptic plasticity failure.

Authors key words:
Alzheimer's disease, amyloid beta precursor, cytoskeleton, Down syndrome, learning, memory, lipoprotein receptor, LTP, neurodegeneration marker, oxidative stress, PHF tau phosphorylation, plaque, phospholipids, synaptic plasticity, secretase, SREBP

Preliminary account:  Soc Neurosci Abstr 2000 26: 181.14.
Soc Neurosci Abstr 2001 27: 23.3

Other related  presentations: see SFN'2001 Meeting Central

Postpublication account:  Neurology 2002 58: 1135

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