This may have been noted before, but a nice summary of Balin's work on Chlamydia pneumoniae and Alzheimer's. Note his discussion of the need for using multple measures (up to 15) and different methodologies in trying to detect a very difficult to detect organism:
I am very excited to present the following article that summarizes Dr. Stratton's recent observations on Chlamydia pneumoniae infection. Putting it together has contributed greatly to my own understanding of Cpn as well as to my appreciation of Dr. Stratton's generosity with his time, and his great depth of knowledge of this area. Thanks to him for his contribution.
Jim KRecent observations by Dr
Recent observations by Dr. Charles Stratton on Chlamydia Pneumoniae (Cpn) Infection
This pre-publication abstract is a remarkable piece of laboratory work. It strengthens the case for Cpn infection especially in MS and Alzheimer's, and other brain diseases.
The two findings I've underlined which seem to have espeical importance is (1) the sensitivity of neuronal cells to infection, as big producers of EB's, and their particular sensitivity to necrosis (tissue death); and (2) the finding in microglial cells that they resist active replicating infection but appear to be potential reservoirs for persistant Cpn.
Neurobiol Aging. 2006 Apr 16; [Epub ahead of print]
Chlamydia pneumoniae infection of brain cells: An in vitro study.
Boelen E, Steinbusch HW, van der Ven AJ, Grauls G, Bruggeman CA, Stassen FR.
Department of Medical Microbiology, CARIM (Cardiovascular Research Institute Maastricht), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Cellular Neuroscience, EURON (European Graduate School of Neurosciences), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Inspired by the suggested associations between neurological diseases and infections, we determined the susceptibility of brain cells to Chlamydia pneumoniae (Cpn). Murine astrocyte (C8D1A), neuronal (NB41A3) and microglial (BV-2) cell lines were inoculated with Cpn. Infection was established by immunofluorescence and real-time PCR at various time points. Productive infection was assessed by transferring medium of infected cells to a detection layer. Finally, apoptosis and necrosis post-infection was determined. Our data demonstrate that the neuronal cell line is highly sensitive to Cpn, produces viable progeny and is prone to die after infection by necrosis. Cpn tropism was similar in an astrocyte cell line, apart from the higher production of extracellular Cpn and less pronounced necrosis. In contrast, the microglial cell line is highly resistant to Cpn as the immunohistochemical signs almost completely disappeared after 24h. Nevertheless, significant Cpn DNA amounts could be detected, suggesting Cpn persistence. Low viable progeny and hardly any necrotic microglial cells were observed. Further research is warranted to determine whether these cell types show the same sensitivity to Cpn in an in vivo setting.
PMID: 16621171 [PubMed - as supplied by publisher]
Brian Balin has done a remarkable job of pursuing a consistent line of research looking at Chlamydia Pneumoniae as a causal source or co-factor in Alzheimer's disease.
Information about Dr. Balin can be found at this link.
Comments he has made about his research can be found at this link. Included is a comment he made which is very reminiscent of Dr. Sriram's answer's to negative studies by other researchers, noting that he, like Sriram, used frozen brain sections and found Cpn DNA, whereas the other researchers used formalin preserved sections and did not find Cpn evidence.
I have culled from Mitchell & Stratton patent #6,884,784 an exhaustive list of diseases where Cpn has been implicated as a possible cause or co-factor (reference: Mitchell & Stratton patent #6,884,784):
Diseases where an association has been discovered between chronic Chlamydia infection of body fluids and/or tissues with several disease syndromes of previously unknown etiology in humans which respond to unique antichlamydial regimens include:
Editorial comment: Strong findings from their research. If you have any of these it suggests to me that at least an empirical course of the combination antibiotic therapy is strongly indicated, with or without serology.
Multiple Sclerosis (MS)
Rheumatoid Arthritis (RA)
Inflammatory Bowel Disease (IBD)
Interstitial Cystitis (IC)
Autonomic nervous dysfunction (AND neural-mediated hypotension);
Pyoderma Gangrenosum (PG)
Chronic Fatigue (CF) and Chronic Fatigue Syndrome (CFS).
Microb Pathog. 2005 Jul 2; [Epub ahead of print]
The load of Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype.
Gerard HC, Wildt KL, Whittum-Hudson JA, Lai Z, Ager J, Hudson AP.
Department of Immunology and Microbiology, Wayne State University School of Medicine, Gordon H. Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA.
Studies from this laboratory have indicated that the intracellular eubacterial respiratory pathogen Chlamydophila (Chlamydia) pneumoniae is commonly found in brain regions displaying characteristic neuropathology in patients with late-onset Alzheimer's disease (AD) but not in congruent samples from non-AD control individuals. In later work, we provided evidence suggesting that some relationship exists between the APOE epsilon4 gene product and the pathobiology of this organism. In the present report, in situ hybridization analyses indicated that the number of C. pneumoniae-infected cells in affected brain regions of epsilon4-bearing AD patients was higher overall than that in congruent brain regions from AD patients lacking that allele. Quantitative real-time PCR analyses of AD brain tissue samples demonstrated that actual bacterial burden in those samples varied over several orders of magnitude, but that samples from epsilon4-bearing patients did have significantly higher bacterial loads than did congruent samples from patients without the allele (ANOVA, p<0.05). These results may explain in part the observations that epsilon4-bearing individuals have a higher risk of developing AD, and that such patients progress more rapidly to cognitive dysfunction than do individuals lacking this allele.