Alzheimer’s disease (AD) is the most common cause of age-related dementia, with a majority of cases having a sporadic, rather than familial, origin. Research suggests neuroinflammation of the brain is linked to the pathogenesis of the disease, however previous studies had not established whether this link was causal.

Kneusel and colleagues set out to investigate this association in a novel mouse model for sporadic AD using polyriboinosinic-polyribocytidilic acid (PolyI:C), a viral mimic that stimulates the immune system.

“It seems likely that chronic inflammation due to infection could be an early event in the development of AD.”
Irene Knuesel, University of Zurich

Based on the similarity between the changes in the immune-challenged mice and the development of AD in humans, this comprehensive study suggests that systemic infections represent a major risk factor for the development of AD. Knuesel and colleagues notably provide the first evidence that a pre-natal systemic immune challenge in mice results in chronic inflammation, increased levels of amyloid precursor protein, tau mislocalisation and cognitive impairments, all of which leave the brain vulnerable to pathological aging and AD. Moreover, a subsequent systemic immune challenge in adulthood further exacerbates the situation leading to neuropathological hallmarks representative of a precursor stage of early AD.

Guojun Bu, professor of neuroscience at the Mayo Clinic, USA and co-Editor-in-Chief of Molecular Neurodegeneration, was one of three judges for the Research Awards in this category, and commended the studies novel observation of “the close relationship between the immune system and the pathogenic process of AD.”

These findings provide compelling evidence for the causative role of systemic immune challenges in the development of AD-like neuropathology and also provides the scientific community with a unique tool, in the PolyI:C mouse model, to investigate the molecular mechanisms underlying early pathophysiological changes in sporadic AD.

“The relationship of inflammatory processes and neurodegeneration is frequently discussed but has not been seriously examined in animal models so far”, noted Research Award judge Amos Korczyn from the department of neurology at Tel Aviv University, Israel. “This study is very comprehensive, including both biochemical and anatomical changes in a systematic study of wild-type and transgenic animals. The work is outstanding and I expect it to be of high impact.”

“It is an honor to have been selected as the winner of the Microbiology, Immunology, Infection and Inflammation category Research Award”, said Oh, lead author of the study and postdoctoral fellow in the laboratory of Julia Segre. The award was presented in May 2013 at the General Meeting of the American Society for Microbiology, Colorado and judged by a panel of eminent scientists and clinicians including Frank Cox, Senior Research Fellow at the London School of Hygiene and Tropical Medicine.

“The quality of research within the microbiology category was outstanding. All the papers I read were clear, well written and made important advances to particular fields and the biomedical sciences in general”, said Cox.

Findings from the winning article mark a significant contribution to the field of microbiology, revealing how an area previously unassociated with major age-related physiological changes – the inner nostril – shows distinct differences in microbial communities depending on pubertal age.

“Studying the diverse communities of microbes in and on our bodies has the potential to help us better understand human health and disease”
Julia Oh, National Human Genome Research Institute

Oh and colleagues examined the bacterial communities inhabiting the skin of healthy children and adults using 16S-rRNA gene sequencing technology. Their results and continued research may help explain why certain conditions, such as pediatric atopic dermatitis, spontaneously resolve with age and how treatments in children for disorders influenced by microbial imbalances could be improved through a better understanding of the microbiome-related differences that arise during maturity.

Oh expressed hopes that receiving the award will “publicize the concept that not only one’s body, physiology, and health develop and evolve over our lives as we age, but there is a corresponding developmental trajectory to our microbial communities that likely has a very direct impact on our health”. Future work in the labs of Segre and Kong will continue to explore this ‘developmental trajectory’, going beyond bacteria and looking at fungal and viral communities innate to the human body.

Read more from Oh about the Award-winning research article in Biome’s Author Q&A here.

“We’re extremely honoured by this award considering all of the wonderful research that is being published at BioMed Central,” said Stedman.

Current dogma states that viruses fall into three groups; RNA viruses, DNA viruses and retroviruses (those that need to be reverse transcribed from RNA into DNA). It is well-established that within each of these groups genetic material can be exchanged between different viruses. In their article however, Stedman and Diemer reveal for the first time that RNA and DNA viruses can also recombine with each other.

           “I have long been fascinated by the simple yet evolutionarily sophisticated nature of viruses”
Geoffrey Diemer, Portland State University

Analysing virus samples isolated from the acidic hot lake, Boiling Springs Lake, USA led to their discovery of a novel viral genome likely to have resulted from a DNA-RNA recombination event between two unrelated viruses. The DNA virus identified was found to encode a major capsid protein of a kind found only in RNA viruses. This unexpected finding received much praise from the Research Award judges, however the means by which it was uncovered was also of note.

“This discovery came from employing a metagenomic approach and it is hard to see how prior approaches could have made the same discovery,” said Laurence Hurst, Professor of Evolutionary Genetics at the University of Bath, UK and one of this year’s judging panel of expert scientists and clinicians. “The paper opens up new avenues in viral research, not least because the mechanism by which the interviral RNA-DNA recombination occurs has yet to be discovered,” remarked Hurst.

         “This work highlights the new route to discovery in virology – the metagenomic path”
Eugene Koonin, co-Editor-in-Chief, Biology Direct

Fellow judge Frank Cox, Senior Research Fellow at the London School of Hygiene and Tropical Medicine, UK similarly echoed the importance of this study. “This is a significant contribution to our understanding of viruses and has implications well outside the immediate finding”. These views were shared by experts in the field who peer reviewed the manuscript and whose attributed reports are freely accessible with the published article online due to the pioneering model of open peer review exercised by Biology Direct.

“This is a truly exciting paper that reports the discovery of a completely unexpected entity,” wrote reviewer Eugene Koonin, Senior Investigator at the National Center for Biotechnology Information, Bethesda, USA. “To my knowledge, such a chimera between RNA and DNA viruses […] has never been observed before.” Reviewer Arcady Mushegian, Professor of Microbiology at the University of Kansas School of Medicine, USA, wrote “This is a fascinating discovery of a novel virus group, suggesting the ancient act of exchange of genetic material between RNA and DNA virus genomes.”

Since publication of the award-winning article, several other groups have also detected the presence of viral genomes formed through interviral RNA-DNA recombination. Stedman is hopeful that “having been selected for such an award will encourage other researchers to venture into this fascinating new territory as well.” You can read more from Stedman about the article in Biome’s Author Q&A here.

BioMed Central’s 7th Annual Research Award is sponsored by antibodies-online.com.