A special May issue of the Journal of Alzheimer’s Disease, 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 the topic of how pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection, which has received little attention in the past.

It appears that during an infection cells generated by inflammatory cells may cause DNA damage. 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 plaque. 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.

This special issue contains a series of reviews from both a historical and recent perspective. The first review shows the importance of chronic inflammation in AD, followed by three articles presenting evidence on the involvement of spirochetes, Chlamydia pneumonia and Herpes simplex virus type 1 in Alzheimer’s disease. These are followed by a review of amyloid proteins, which occur in many cellular forms in Eukaryotes and Prokaryotes.

The editors feel that treatment of a bacterial infection and associated viral infection may result in regression and, if started early, prevention of disease. The impact on reducing health-care costs would be substantial.

Donna Kritz-Silverstein, PhD, adjunct professor, Family & Preventive Medicine, University of California, San Diego, and colleagues, studied effects of DHEA supplements on 110 men and 115 women, between 55-85. The participants received either 50 mg doses of DHEA or a look-a-like placebo. Six cognitive function tests were given and measures of depression, perceptions of physical and emotional health, life satisfaction and sexual function were recorded at the beginning of the study and again at the conclusion of the study one year later.

Although the group receiving DHEA had returned to youthful levels of the drug there were no benefits for cognitive function. Also, there were no differences seen between those taking DHEA and those taking placebo in quality-of-life measurement scores.

Previous clinical trials examining the effects of DHEA supplementation on cognitive function and quality-of-life have inconsistent results, with some showing positive effects and others showing no effect. However, these trials used small sample sizes, were of short duration (generally 2 weeks to 4 months) and did not include older men and women who were at an age when memory loss and cognitive impairment become more apparent. Also, unlike the participants in the majority of previous studies, the participants in this study were not selected for lower levels of DHEA, meaning the results reflect what would be found in the general population.

The study is published in the Journal of American Geriatrics Society.

William Bowers, associate professor of neurology, microbiology, and immunology, University of Rochester Medical Center, believes he and his co-workers have demonstrated a way to create a potent, but safe, version of a vaccine that causes an immune response that prevents Alzheimer’s disease and memory deficits.

Mice, genetically engineered to develop Alzheimer’s, were given a vaccine that caused the immune system to target amyloid beta proteins–considered to be the cause for Alzheimer’s disease. Previous to the 10-month study the mice were trained to navigate through a maze. During the study the mice were timed on how long it took to successfully get to the maze’s exit. The maze test results excited researchers because it indicated their vaccine was able to prompt the immune system to successfully remove amyloid beta before it mutated into the Alzheimer’s disease causing form.

A number of studies will be needed to meet regulatory requirements before the vaccine can be tested on humans, which is expected to take at least 3 years.

Shirley E. Poduslo, PhD, neuroscientist, Medical College of Georgia Schools of Medicine and Graduate Studies, studied the genetic profile of 2 large Georgia families with high rates of late-onset Alzheimer’s disease. Poduslo was shocked when she found that the single nucleotide polymorphisms (SNP) occurred 9 out of 10 times in affected family members. SNPs also were found in the DNA of 36% of 200 late-onset patients stored in the Alzheimer’s DNA Bank.

The gene variation was in the TRPC4AP; part of a large family of genes that is not well-studied, but believed to regulate calcium. Calcium is needed throughout the body and its dysregulation can result in inflammation, nerve cell death and possibly plaque formation.

The next step is to identify the specific genetic mutation responsible. The mutation could be a deletion of some of the nucleotides, an insertion into the gene, or something that prevents the gene from duplicating correctly.

James Shorter, PhD, Assistant Professor of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, has made a surprising discovery. A small molecule, called DAPH, can be used to target the areas that hold the amyloid fibers together and convert the fibers to a form that makes them unable to grow. DAPH accomplishes this remarkable goal by preventing growth from the ends of the fibers.

The DAPH molecule remodels the fiber architecture, which is something researchers have not been able to accomplish before. DAPH was originally found in a screen of small molecules that reduce amyloid-beta toxicity by Vernon Ingram, Massachusetts Institute of Technology (MIT), and co-researcher.

When a small amount of amyloid (or prion) fiber is added to the normal form of the protein it is converted to the fiber form. However, when DAPH is added the conversion process is prevented and essentially stops fiber formation in its tracks.

Some types of amyloids may be helpful–like in formation of memories–so, researchers are now looking for a way to selectively choose which type of amyloid protein is affected.

The Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT) Research Group studied 2,117 individuals, 70 years and older, who have a family history of Alzheimer’s. For 3 years the participants were tested annually for cognitive function.

• 29% were given 200 milligrams of celecoxib twice daily.
• 28% were given 220 milligrams of naproxen sodium twice daily.
• 43% were given a placebo.

Six months after the study was terminated (because another study found celecoxib increased cardiovascular risks) the use of NSAIDs did not show a protective effect and in fact naproxen users had a lower cognitive assessment score when compared to celecoxib and the placebo.

Why the difference? Several explanations were offered:

• Previous studies analyzed behavior rather than assigning subjects to treatment groups.
• Factors not measured in the previous study may have confounded or affected the results.
• The findings of this study apply only to celecoxib and naproxen.
• NSAIDs may be protective only when given several years before the decline of cognitive function.

Researchers conclude that naproxen and celecoxib should not be used for the prevention of Alzheimer’s disease.

In an article published in the Annals of the Rheumatic Diseases a study reports that researchers compared 136 women with rheumatoid arthritis with 544 women of a similar age without the disease. They found that those who had breast fed for longer were much less likely to get rheumatoid arthritis.

Women who had breastfed for 13 months or more were half as likely to get rheumatoid arthritis as those who had never breast fed. Those who had breast fed for one to 12 months were 25% less likely to get the disease.

The proportion of women breast feeding for more than six months has increased dramatically over the past 30 years. The authors concluded that it was difficult to say whether there was a connection between higher rates of breast feeding and a corresponding fall in the number of women affected by rheumatoid arthritis, but that the results of the study provided yet another reason why women should continue breast feeding.

A recent May Clinic study surprises practitioners of both systems that they are fundamentally similar despite the differences in approach to treat pain.

Peter Dorsher, MD, Department of Physical Medicine and Rehabilitation, Mayo Clinic, Jacksonville, Florida, found in a recent study that at least 92% of common trigger points anatomically correspond with acupoints; that those used to treat pain corresponded more than 95% of the time.

Dorsher points out that myofascial pain treatment was a rediscovery of a system discovered 2,000 years before by the Chinese. Myofascial trigger-point therapy has 255 regions described by the Trigger Point Manual, whereas classic Chinese acupuncture has 361 acupoints that target specific organs or pain problems.

The study was funded by the Mayo Clinic.

Nikolaus Grigorieff, biophysicist, Brandeis University, along with researchers at Leibniz Institut, Jena, Germany, have successfully created an A-beta peptide 3-D image. Grigorieff, and colleagues, overcame the barrier to determining the structure of A-beta fibrils by generating them in a test tube under conditions that reduce the variability between fibrils, then selecting about 200 images of fibrils that were similar and averaging them on a computer.

Researchers plan to create a 3-D image that shows where all of the amino acids are located in hopes to learn more about the chemical and biological properties of A-beta Fibrils to have a better understanding of their role in Alzheimer’s disease.

Jon-Kar Zubieta, MD, PhD, University of Michigan, reports that depression is rooted in genetic and molecular factors and are unique for each individual. Using PET (positron emission tomography) scans, Zubieta studied patients who met the criteria for major depression, but had not yet received treatment for it. Those scans were compared with scans of non-depressed volunteers.

Serotonin levels were linked to depression as were the ‘feel-good’ (5HT1a) receptor concentrations. The worse the subject scored on the depression assessment the fewer ‘feel-good’ receptors they had. He also found that there was a direct relationship between the effectiveness of medication used to treat depression and the number of ‘feel-good’ receptors. The fewer the ‘feel-good’ receptors the less likely medication was going to relieve signs of depression.