Perspectives on the Intracellular Bacterium Chlamydia pneumoniae in Late-Onset Dementia

Purpose of Review Chronic diseases remain a daunting challenge for clinicians and researchers alike. While difficult to completely understand, most chronic diseases, including late-onset dementias, are thought to arise as an interplay between host genetic factors and environmental insults. One of the most diverse and ubiquitous environmental insults centers on infectious agents. Associations of infectious agents with late-onset dementia have taken on heightened importance, including our investigations of infection by the intracellular respiratory bacterium, Chlamydia pneumoniae (Cpn), in late-onset dementia of the Alzheimer’s type. Recent Findings Over the last two decades, the relationship of this infection to pathogenesis in late-onset dementia has become much clearer. This clarity has resulted from applying contemporary molecular genetic, biochemical, immunochemical, and cell culture techniques to analysis of human brains, animal models, and relevant in vitro cell culture systems. Data from these studies, taken in aggregate form, now can be applied to evaluation of proof of concept for causation of this infection with late-onset disease. In this evaluation, modifications to the original Koch postulates can be useful for elucidating causation. Summary All such relevant studies are outlined and summarized in this review, and they demonstrate the utility of applying modified Koch postulates to the etiology of late-onset dementia of the Alzheimer’s type. Regardless, it is clear that even with strong observational evidence, in combination with application of modifications of Koch’s postulates, we will not be able to conclusively state that Cpn infection is causative for disease pathogenesis in late-onset dementia. Moreover, this conclusion obtains as well for the putative causation of this condition by other pathogens, including herpes simplex virus type 1, Borrelia burgdorferi, and Porphyromonas gingivalis

Supergravity Computations without Gravity Complications

The conformal compensator formalism is a convenient and versatile representation of supergravity (SUGRA) obtained by gauge fixing conformal SUGRA. Unfortunately, practical calculations often require cumbersome manipulations of component field terms involving the full gravity multiplet. In this paper, we derive an alternative gauge fixing for conformal SUGRA which decouples these gravity complications from SUGRA computations. This yields a simplified tree-level action for the matter fields in SUGRA which can be expressed compactly in terms of superfields and a modified conformal compensator. Phenomenologically relevant quantities such as the scalar potential and fermion mass matrix are then straightforwardly obtained by expanding the action in superspace.Comment: 10 pages; v2: references update

Emerging Microbial and Viral Infections of the Central Nervous System

This review focuses on emerging viral and bacterial infections in the human central nervous system (CNS) that are responsible for significant global morbidity and mortality. These infections include those responsible for acute neurological disease such as meningitis and encephalitis as well those associated with chronic neurodegenerative conditions. Recent changes in climate conditions and pollution have been precipitating factors leading to the emergence of many of these pathogenic organisms. In addition, increased urbanization, global travel, life span, and exposure to new vectors have promoted the organisms’ spread across the globe. Categorization of many of these organisms includes identification of new species, recognition of new tropism to the CNS, spread into naïve demographic areas, increased human contact with zoonotic repositories including insect vectors, and reemergence of well-known organisms. These mechanisms are highlighted for the different organisms included in this review. Other mechanisms for CNS emergence such as genetic mutation of the organisms and immunosuppression and/or immunosenescence of the host are addressed. Viral and bacterial infections in chronic neurodegenerative diseases traditionally not thought to be infectious are considered. Although this review cannot be all-inclusive, the organisms included represent a sampling of extremely important microbes and their role in CNS pathogenesis in the twenty-first century

Spontaneous rotating vortex rings in a parametrically driven polariton fluid

We present the theoretical prediction of spontaneous rotating vortex rings in a parametrically driven quantum fluid of polaritons -- coherent superpositions of coupled quantum well excitons and microcavity photons. These rings arise not only in the absence of any rotating drive, but also in the absence of a trapping potential, in a model known to map quantitatively to experiments. We begin by proposing a novel parametric pumping scheme for polaritons, with circular symmetry and radial currents, and characterize the resulting nonequilibrium condensate. We show that the system is unstable to spontaneous breaking of circular symmetry via a modulational instability, following which a vortex ring with large net angular momentum emerges, rotating in one of two topologically distinct states. Such rings are robust and carry distinctive experimental signatures, and so they could find applications in the new generation of polaritonic devices.Comment: 6 pages, 4 figure

Editorial: Infection, inflammation, and neurodegeneration: A critical path to Alzheimer\u27s disease, Volume II.

No abstract availabl

Chlamydia pneumoniae Infection of Monocytes in vitro Stimulates Innate and Adaptive Immune Responses Relevant to those in Alzheimer\u27s Disease.

Background: Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder in which infection with Chlamydia pneumoniae (Cpn) has been associated. Cpn is an obligate intracellular respiratory pathogen that may enter the central nervous system (CNS) following infection and trafficking of monocytes through the blood-brain barrier. Following this entry, these cells may secrete pro-inflammatory cytokines and chemokines that have been identified in the AD brain, which have been thought to contribute to AD neurodegeneration. The objectives of this work were: (i) to determine if Cpn infection influences monocyte gene transcript expression at 48 hours post-infection and (ii) to analyze whether pro-inflammatory cytokines are produced and secreted from these cells over 24 to 120 hours post-infection. Methods: Gene transcription was analyzed by RT-PCR using an innate and adaptive immunity microarray with 84 genes organized into 5 functional categories: inflammatory response, host defense against bacteria, antibacterial humoral response, septic shock, and cytokines, chemokines and their receptors. Statistical analysis of the results was performed using the Student\u27s t-test. P-values ≤ 0.05 were considered to be significant. ELISA was performed on supernatants from uninfected and Cpn-infected THP1 monocytes followed by statistical analysis with ANOVA. Results: When Cpn-infected THP1 human monocytes were compared to control uninfected monocytes at 48 hours post-infection, 17 genes were found to have a significant 4-fold or greater expression, and no gene expression was found to be down-regulated. Furthermore, cytokine secretion (IL-1ß, IL-6, IL-8) appears to be maintained for an extended period of infection. Conclusions: Utilizing RT-PCR and ELISA techniques, our data demonstrate that Cpn infection of THP1 human monocytes promotes an innate immune response and suggests a potential role in the initiation of inflammation in sporadic/late-onset Alzheimer\u27s disease

Evaluation of Smell and miRNA Biomarkers in Alzheimer’s Disease (AD)

Abstract and poster under embargo until May 31, 2019

Role of Microbes in the Development of Alzheimer\u27s Disease: State of the Art - An International Symposium Presented at the 2017 IAGG Congress in San Francisco.

This article reviews research results and ideas presented at a special symposium at the International Association of Gerontology and Geriatrics (IAGG) Congress held in July 2017 in San Francisco. Five researchers presented their results related to infection and Alzheimer\u27s disease (AD). Prof. Itzhaki presented her work on the role of viruses, specifically HSV-1, in the pathogenesis of AD. She maintains that although it is true that most people harbor HSV-1 infection, either latent or active, nonetheless aspects of herpes infection can play a role in the pathogenesis of AD, based on extensive experimental evidence from AD brains and infected cell cultures. Dr. Miklossy presented research on the high prevalence of bacterial infections that correlate with AD, specifically spirochete infections, which have been known for a century to be a significant cause of dementia (e.g., in syphilis). She demonstrated how spirochetes drive senile plaque formation, which are in fact biofilms. Prof. Balin then described the involvement of brain tissue infection by th

Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain

<p>Abstract</p> <p>Background</p> <p>Sporadic late-onset Alzheimer's disease (AD) appears to evolve from an interplay between genetic and environmental factors. One environmental factor that continues to be of great interest is that of <it>Chlamydia pneumoniae </it>infection and its association with late-onset disease. Detection of this organism in clinical and autopsy samples has proved challenging using a variety of molecular and histological techniques. Our current investigation utilized immunohistochemistry with a battery of commercially available anti-<it>C. pneumoniae </it>antibodies to determine whether <it>C. pneumoniae </it>was present in areas typically associated with AD neuropathology from 5 AD and 5 non-AD control brains.</p> <p>Results</p> <p>Immunoreactivity for <it>C. pneumoniae </it>antigens was observed both intracellularly in neurons, neuroglia, endothelial cells, and peri-endothelial cells, and extracellularly in the frontal and temporal cortices of the AD brain with multiple <it>C. pneumoniae</it>-specific antibodies. This immunoreactivity was seen in regions of amyloid deposition as revealed by immunolabeling with two different anti-beta amyloid antibodies. Thioflavin S staining, overlaid with <it>C. pneumoniae </it>immunolabeling, demonstrated no direct co-localization of the organism and amyloid plaques. Further, the specificity of <it>C. pneumoniae </it>labeling of AD brain sections was demonstrated using <it>C. pneumoniae </it>antibodies pre-absorbed against amyloid β 1-40 and 1-42 peptides.</p> <p>Conclusions</p> <p>Anti-<it>C. pneumoniae </it>antibodies, obtained commercially, identified both typical intracellular and atypical extracellular <it>C. pneumoniae </it>antigens in frontal and temporal cortices of the AD brain. <it>C. pneumoniae</it>, amyloid deposits, and neurofibrillary tangles were present in the same regions of the brain in apposition to one another. Although additional studies are required to conclusively characterize the nature of Chlamydial immunoreactivity in the AD brain, these results further implicate <it>C. pneumoniae </it>infection with the pathogenesis of Alzheimer's disease.</p