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Researchers explore the emerging role of infection in Alzheimer's disease

May 23, 2008

A number of chronic diseases are in fact caused by one or more infectious agents. For example, stomach ulcers are caused by Helicobacter pylori, chronic lung disease in newborns and chronic asthma in adults are both caused by Mycoplasmas and Chlamydia pneumonia, while some other pathogens have been associated with atherosclerosis. The realization that pathogens can produce slowly progressive chronic diseases has opened new lines of research into Alzheimer's disease.

In a special issue of the Journal of Alzheimer's Disease published May 2008, guest editors Judith Miklossy, from The University of British Columbia, and Ralph N. Martins, from Edith Cowan University and Hollywood Private Hospital, Perth, Western Australia, and a group of experts explore this exciting topic.

Alzheimer's disease (AD), the most frequent cause of dementia, is a form of amyloidosis. It has been known for a century that dementia, brain atrophy and amyloidosis can be caused by chronic bacterial infections, namely by Treponema pallidum in the atrophic form of general paresis in syphilis. Bacteria and viruses are powerful stimulators of inflammation. It was suggested by Alois Alzheimer and his colleagues a century ago that microorganisms may be contributors in the generation of senile plaques in AD.

The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells may cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the organism can persist in the infected tissues and cause chronic inflammation and amyloid deposition. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors and nutrition are critical determinants of disease expression as well.

In this special issue a series of reviews draws attention to both historic and recent observations related to this emerging field of AD research. The first review shows the importance of chronic inflammation in AD, followed by three articles presenting evidence on the involvement of spirochetes, Chlamydia pneumoniae and Herpes simplex virus type 1 in AD. These are followed by a review of amyloid proteins, which occur in many cellular forms in Eukaryotes and Prokaryotes.

The link between several viral and bacterial infections and the most significant genetic factor for AD, APOE å4, is discussed in the next review. The link between excessive or misplaced iron and a variety of neurodegenerative diseases and infection is reviewed in the final article.

According to Miklossy and Martins, "The historic and new observations reviewed in this special issue clearly show that high priority should be given for further research in this field as it may have major implications for public health, treatment, and prevention as adequate anti-bacterial and anti-viral drugs are available. Treatment of a bacterial infection and associated viral infection may result in regression and, if started early, prevention of disease. The impact on reducing healthcare costs would be substantial."

IOS Press