15 March 2016
A landmark Editorial issued by 33 senior scientists and clinicians from a dozen countries across the world has been published in the highly regarded peer-reviewed journal, Journal of Alzheimer's Disease. This major call for action is based on substantial evidence indicating that some microbes – a specific virus and particular bacteria – are likely major causes of the disease.
Almost all research in the field has focused on alternative hypotheses – over 400 clinical trials of such anti-Alzheimer agents have been carried out, but all have failed.
Although the potential involvement of microbes in Alzheimer disease has been known for decades, this work has been dismissed as controversial. Opposition to the idea that microbes might be involved resembles the fierce resistance to studies some years ago demonstrating that viruses cause some types of cancer and a bacterium causes stomach ulcers.
Now, as then, the opposition has been based on opinion rather than on science. Those earlier concepts ultimately proved to be valid, leading to successful clinical trials and the subsequent development of appropriate treatments.
The Editorial stresses the pressing need for further research into the link between infection and Alzheimer disease. The experts argue that clinical trials of antimicrobial agents to treat Alzheimer's disease are now warranted.
Alzheimer disease (AD) is a debilitating disorder, both for the individual and their close families. Despite years of effort no effective treatment is available.
The disease was first recorded by physicians in central Europe, including Alois Alzheimer, and by others at the time. Puzzled by this disease, they looked at brain specimens, and saw aggregates of clumped protein. These had a shiny appearance resembling rice grains (Latin, amylum): these were named beta-amyloid.
This has been widely confirmed. But do (i) these amyloid deposits in brain cause the disease, or (ii) are they a consequence of the disease?
Most bioscience research over the past 20 years has focused on the first question. This question has now been answered. First, normal elderly people can have large amounts of amyloid, but be as sharp as youngsters. Second, large clinical trials, for example using immunological methods to remove amyloid, have been able to purge the brain of amyloid, but the Alzheimer patients do not get better. In fact, 10% get worse. Therefore, amyloid does not cause the disease.
Is then amyloid a consequence of disease?
This seems to be the case. It has been known for years that infection of mice with viruses leads to deposition of amyloid. In humans, individuals suffering from brain infection with viruses such as HIV and herpes develop amyloid deposits.
We are now beginning to understand why the brain makes amyloid. Work at Harvard and elsewhere has shown that the amyloid protein is a defense mechanism, and kills microbes including viruses, bacteria, and yeasts.
Efforts worldwide to target amyloid as a cause of disease were an essential step along the path because they demonstrated that amyloid does not cause Alzheimer disease. Now it is time to move on: and address whether combating microbes might provide respite for Alzheimer patients.
It is very important to recognize that Alzheimer is not an infectious disease like chickenpox. All of us are persistently infected with infectious agents, such as herpesviruses, but these for the most part are silent. Only with aging and decline of the immune system do these become reactivated. But there are tools to combat proliferation, and several potent antimicrobial drugs are available. These now warrant testing in Alzheimer disease.
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NOTES FOR EDITORS
Itzhaki, R. et al. (2016) Microbes and Alzheimer disease. Journal of Alzheimer Disease, http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160152.
Full text of the editorial is available to credentialed journalists upon request by contacting Daphne Watrin at +31 20 688 3355 or email@example.com. Journalists who wish to reach the signatories for comment should contact Ruth Itzhaki at +44 01865 250853 or firstname.lastname@example.org.
George Perry, PhD
Editor-in-Chief, Journal of Alzheimer's Disease
Dean and Professor of Biology, The University of Texas at San Antonio
Tel: +1 210 458 4450
Fax:+1 210 458 4445
Tel: +31 20 688 3355
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ABOUT THE JOURNAL OF ALZHEIMER’S DISEASE
The Journal of Alzheimer's Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 4.151 according to Thomson Reuters' 2014 Journal Citation Reports. The Journal is published by IOS Press (www.iospress.com).
ABOUT IOS PRESS
Commencing its publishing activities in 1987, IOS Press (www.iospress.nl) is headquartered in Amsterdam with satellite offices in the USA, Germany, India and China and serves the information needs of scientific and medical communities worldwide. IOS Press now publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.