Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain
Open accessAbstract
Background: 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 Chlamydia pneumoniae 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-C. pneumoniae antibodies to determine whether C. pneumoniae was present in areas typically associated with AD neuropathology from 5 AD and 5 non-AD control brains. Results: Immunoreactivity for C. pneumoniae 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 C. pneumoniae-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 C. pneumoniae immunolabeling, demonstrated no direct co-localization of the organism and amyloid plaques. Further, the specificity of C. pneumoniae labeling of AD brain sections was demonstrated using C. pneumoniae antibodies pre-absorbed against amyloid β 1-40 and 1-42 peptides. Conclusions: Anti-C. pneumoniae antibodies, obtained commercially, identified both typical intracellular and atypical extracellular C. pneumoniae antigens in frontal and temporal cortices of the AD brain. C. pneumoniae, 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 C. pneumoniae infection with the pathogenesis of Alzheimer's disease.
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C. pneumoniae antigens have been detected inside both astrocytes and microglia in post-mortem human brains.
“C. pneumoniae antigens have been detected inside both astrocytes and microglia in post-mortem human brains9,11,67,68.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [67]
The Results (page not available) report intracellular C. pneumoniae antigen labeling in neuroglia in human Alzheimer’s disease brain tissue. They do not identify the labeled neuroglia separately as both astrocytes and microglia. The Background says those cell types are susceptible to infection, but that does not establish antigen detection inside each in the examined brains. (LLM, conf=0.84)
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Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859 · see citing works
The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Soscia, S. J., Kirby, J. E., Washicosky, K. J., Tucker, S. M., Ingelsson, M., Hyman, B., Burton, M. A., Goldstein, L. E., Duong, S., Tanzi, R. E., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009505 · Cited by 1,060 · see citing works
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031 · see citing works
Age, Neuropathology, and Dementia
Savva, G. M., Wharton, S. B., Ince, P. G., Forster, G., Matthews, F. E., & Brayne, C. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0806142 · Cited by 900 · see citing works
Epidemiology and Clinical Characteristics of Community-Acquired Pneumonia in Hospitalized Children
Michelow, I. C., Olsen, K. D., Lozano, J., Rollins, N. K., Duffy, L. B., Ziegler, T. T., Kauppila, J., Leinonen, M., & McCracken, G. H. (2004) · PEDIATRICS · doi:10.1542/peds.113.4.701 · Cited by 709 · see citing works
Takahashi, R. H., Milner, T. A., Li, F., Nam, E. E., Edgar, M. A., Yamaguchi, H., Beal, M. F., Xu, H., Greengard, P., & Gouras, G. K. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64463-x · Cited by 706 · see citing works
Herpes simplex virus type 1 in brain and risk of Alzheimer's disease
Itzhaki, R. F., Lin, W., Shang, D., Wilcock, G. K., Faragher, B. E., & Jamieson, G. A. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10149-5 · Cited by 671 · see citing works
Rasmussen, S. J., Eckmann, L., Quayle, A. J., Shen, L., Zhang, Y., Anderson, D. J., Fierer, J., Stephens, R. S., & Kagnoff, M. F. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119136 · Cited by 514 · see citing works
Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain
Balin, B. J., Gérard, H. C., Arking, E. J., Appelt, D. M., Branigan, P. J., Abrams, J. T., Whittum-Hudson, J. A., & Hudson, A. P. (1998) · Medical Microbiology and Immunology · doi:10.1007/s004300050071 · Cited by 506 · see citing works
Self-citationMechanisms of host cell exit by the intracellular bacterium Chlamydia
Hybiske, K., & Stephens, R. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703218104 · Cited by 489 · see citing works
Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques
Wozniak, M., Mee, A., & Itzhaki, R. (2009) · The Journal of Pathology · doi:10.1002/path.2449 · Cited by 464 · see citing works
Zhong, G., Fan, P., Ji, H., Dong, F., & Huang, Y. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.8.935 · Cited by 373 · see citing works
Intraneuronal Aβ accumulation and origin of plaques in Alzheimer's disease
Gouras, G. K., Almeida, C. G., & Takahashi, R. H. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.022 · Cited by 338 · see citing works
Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity
Friedrich, R. P., Tepper, K., Rönicke, R., Soom, M., Westermann, M., Reymann, K., Kaether, C., & Fändrich, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904532106 · Cited by 303 · see citing works
Lue, L. F., Brachova, L., CIVIN, W. H., & Rogers, J. (1996) · PubMed · Cited by 299 · see citing works
Lue, L.-F., Brachova, L., Civin, H. W., & Rogers, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199655100-00008 · Cited by 246 · cited 1× · see citing works
“These cytokine responses to infection parallel similar responses to amyloid accumulation [40].”
BackgroundChlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice
Little, C. S., Hammond, C. J., MacIntyre, A., Balin, B. J., & Appelt, D. M. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00127-1 · Cited by 243 · see citing works
Self-citationChlamydia Inhibit Host Cell Apoptosis by Degradation of Proapoptotic BH3-only Proteins
Fischer, S. F., Vier, J., Kirschnek, S., Klos, A., Hess, S., Ying, S., & Häcker, G. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040402 · Cited by 202 · see citing works
Chlamydia pneumoniaeand atherosclerosis
Belland, R. J., Ouellette, S. P., Gieffers, J., & Byrne, G. I. (2004) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00352.x · Cited by 199 · see citing works
Infiltration of the brain by pathogens causes Alzheimer’s disease
Itzhaki, R. F., Wozniak, M. A., Appelt, D. M., & Balin, B. J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.021 · Cited by 188 · see citing works
Self-citation<i>Chlamydophila (Chlamydia) pneumoniae</i>in the Alzheimer's brain
Gérard, H. C., Dreses-Werringloer, U., Wildt, K. S., Deka, S., Oszust, C., Balin, B. J., Frey, W. H., Bordayo, E. Z., Whittum-Hudson, J. A., & Hudson, A. P. (2006) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2006.00154.x · Cited by 186 · see citing works
Self-citationEarly Olfactory Involvement in Alzheimer’s Disease
Christen‐Zaech, S., Kraftsik, R., Pillevuit, O., Kiraly, M., Martins, R. N., Khalili, K., & Judith Miklossy, A. (2003) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100002389 · Cited by 184 · see citing works
Miklossy, J., Khalili, K., Gern, L., Ericson, R. L., Darekar, P., Bolle, L., Hurlimann, J., & Paster, B. J. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2004-6608 · Cited by 163 · see citing works
Chlamydia pneumoniae Multiply in Neutrophil Granulocytes and Delay Their Spontaneous Apoptosis
van Zandbergen, G., Gieffers, J., Kothe, H., Rupp, J., Bollinger, A., Aga, E., Klinger, M. H. F., Brade, H., Dalhoff, K., Maass, M., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1768 · Cited by 151 · see citing works
Alzheimerʼs disease—a spirochetosis?
Miklossy, J. (1993) · Neuroreport · doi:10.1097/00001756-199307000-00002 · Cited by 137 · see citing works
Alzheimer Disease -- A Spirochetosis?
Judith Miklossy, A. (1994) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4615-8149-9_7 · Cited by 130 · see citing works
MacIntyre, A., Abramov, R., Hammond, C. J., Hudson, A. P., Arking, E. J., Little, C. S., Appelt, D. M., & Balin, B. J. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10519 · Cited by 98 · see citing works
Self-citationPhysiological Roles of Amyloid-?? and Implications for its Removal in Alzheimer???s Disease
Bishop, G. M., & Robinson, S. R. (2004) · Drugs & Aging · doi:10.2165/00002512-200421100-00001 · Cited by 94 · see citing works
D’Andrea, M. R., Nagele, R. G., Wang, H.-Y., & Lee, D. H. S. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00875-3 · Cited by 76 · see citing works
Alzheimer's disease: An olfactory connection?
Mann, D. M. A., Tucker, C. M., & Yates, P. O. (1988) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(88)90058-9 · Cited by 72 · see citing works
MacIntyre, A., Hammond, C. J., Little, C. S., Appelt, D. M., & Balin, B. J. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11470.x · Cited by 68 · see citing works
Self-citationGieffers, J., Pohl, D., Treib, J., Dittmann, R., Stephan, C., Klotz, K.-F., Hanefeld, F. A., Solbach, W., Haass, A., & Maass, M. (2001) · Annals of Neurology · doi:10.1002/ana.1020 · Cited by 66 · see citing works
Dreses‐Werringloer, U., Bhuiyan, M., Zhao, Y., Gérard, H. C., Whittum‐Hudson, J. A., & Hudson, A. P. (2008) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2008.07.002 · Cited by 54 · see citing works
Du, C., Yao, S., Ljunggren‐Rose, A., & Sriram, S. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020393 · Cited by 52 · see citing works
Chlamydia pneumoniae infection of brain cells: An in vitro study
Boelen, E., Steinbusch, H. W. M., van der Ven, A. J. A. M., Grauls, G., Bruggeman, C. A., & Stassen, F. R. M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.02.014 · Cited by 46 · see citing works
Campbell, L. A., & Kuo, C. (2003) · Seminars in Respiratory Infections · doi:10.1053/srin.2003.50006 · Cited by 44 · see citing works
Inhibition of apoptosis in neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae
Appelt, D. M., Roupas, M. R., Way, D. S., Bell, M. G., Albert, E. V., Hammond, C. J., & Balin, B. J. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-13 · Cited by 39 · see citing works
Self-citationSriram, S., Ljunggren‐Rose, A., Yao, S., & Whetsell, W. O. (2005) · The Journal of Infectious Diseases · doi:10.1086/431518 · Cited by 37 · see citing works
Little, C. S., Bowe, A., Lin, R., Litsky, J., Fogel, R. M., Balin, B. J., & Fresa-Dillon, K. L. (2005) · Infection and Immunity · doi:10.1128/iai.73.3.1723-1734.2005 · Cited by 35 · see citing works
Self-citationVikatmaa, P., Lajunen, T. K., Ikonen, T. S., Pussinen, P. J., Lepäntalo, M., Leinonen, M., & Saikku, P. (2009) · Cardiovascular Pathology · doi:10.1016/j.carpath.2008.10.012 · Cited by 28 · see citing works
Fernández-Obregón, A. C., & Patton, D. L. (2007) · PubMed · Cited by 27 · see citing works
Chlamydia pneumoniae antibodies in various subtypes of ischemic stroke in Indian patients
Bandaru, V. C. S. S., Laxmi, V., Neeraja, M., Alladi, S., Meena, A., Borgohain, R., Keerthi, A. S., & Kaul, S. (2008) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.05.008 · Cited by 26 · see citing works
Kammerman, E. M., Neumann, D. M., Ball, M. J., Lukiw, W. J., & Hill, J. M. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.07.033 · Cited by 24 · see citing works
Chlamydiae Host Cell Interactions Revealed Using DNA Microarrays
Mahony, J. B. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb05952.x · Cited by 23 · see citing works
Characterization of Antiapoptotic Activities of Chlamydia pneumoniae in Infected Cells
Fischer, S. F., & Häcker, G. A. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1299.105 · Cited by 16 · see citing works
Stuart, E. S., Troidle, K. M., & MacDonald, A. (1994) · Current Microbiology · doi:10.1007/bf01569052 · Cited by 12 · see citing works
Uptake and intra-inclusion accumulation of exogenous immunoglobulin by Chlamydia-infected cells
Pollack, D. V., Croteau, N. L., & Stuart, E. S. (2008) · BMC Microbiology · doi:10.1186/1471-2180-8-213 · Cited by 5 · see citing works
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Interactions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900 · see citing works
Association between periodontal pathogens and systemic disease
Bui, F. Q., Almeida-da-Silva, C. L. C., Huynh, B. C., Trinh, A., Liu, J., Woodward, J., Asadi, H., & Ojcius, D. M. (2019) · Biomedical Journal · doi:10.1016/j.bj.2018.12.001 · Cited by 832 · see citing works
Brain-Gut-Microbiota Axis in Alzheimer’s Disease
Kowalski, K., & Mulak, A. (2019) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm18087 · Cited by 826 · see citing works
Poole, S., Singhrao, S. K., Kesavalu, L. N., Curtis, M. A., & Crean, S. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121918 · Cited by 599 · see citing works
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease
Kesika, P., Suganthy, N., Sivamaruthi, B. S., & Chaiyasut, C. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118627 · Cited by 479 · see citing works
The Infectious Etiology of Alzheimer’s Disease
Sochocka, M., Zwolińska, K., & Leszek, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313122937 · Cited by 399 · see citing works
Zhan, X., Stamova, B. S., & Sharp, F. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00042 · Cited by 354 · see citing works
The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology
Xie, J., Van Hoecke, L., & Vandenbroucke, R. E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.796867 · Cited by 324 · see citing works
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease
Brothers, H. M., Gosztyla, M. L., & Robinson, S. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00118 · Cited by 314 · see citing works
Infectious Agents and Neurodegeneration
Chiara, G. D., Marcocci, M. E., Sgarbanti, R., Civitelli, L., Ripoli, C., Piacentini, R., Garaci, E., Grassi, C., & Palamara, A. T. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8320-7 · Cited by 231 · see citing works
The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment
Varesi, A., Pierella, E., Romeo, M., Piccini, G. B., Alfano, C., Bjørklund, G., Oppong, A., Ricevuti, G., Esposito, C., Chirumbolo, S., et al. (2022) · Nutrients · doi:10.3390/nu14030668 · Cited by 225 · see citing works
Emerging role of gut microbiota dysbiosis in neuroinflammation and neurodegeneration
Solanki, R., Karande, A. A., & Ranganathan, P. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1149618 · Cited by 192 · see citing works
Bacterial Infection and Alzheimer's Disease: A Meta-Analysis
Maheshwari, P., & Eslick, G. D. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-140621 · Cited by 183 · see citing works
Can oral infection be a risk factor for Alzheimer's disease?
Olsen, I., & Singhrao, S. K. (2015) · Journal of Oral Microbiology · doi:10.3402/jom.v7.29143 · Cited by 182 · see citing works
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175 · see citing works
Teixeira, F. B., Saito, M. T., MATHEUS, F. C., Prediger, R. D., Yamada, E. S., Maia, C. D. S. F., & Lima, R. R. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00327 · Cited by 175 · see citing works
Do infections have a role in the pathogenesis of Alzheimer disease?
Itzhaki, R. F., Golde, T. E., Heneka, M. T., & Readhead, B. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0323-9 · Cited by 173 · see citing works
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Hill, J. M., Clément, C., Pogue, A. I., Bhattacharjee, S., Zhao, Y., & Lukiw, W. J. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00127 · Cited by 169 · see citing works
Kell, D. B., & Pretorius, E. (2015) · Integrative Biology · doi:10.1039/c5ib00158g · Cited by 160 · see citing works
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Mawanda, F., & Wallace, R. B. (2013) · Epidemiologic Reviews · doi:10.1093/epirev/mxs007 · Cited by 151 · see citing works
Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature
Lathe, R., Tsitrina, A. A., & Kotelevtsev, Y. V. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-36 · Cited by 136 · see citing works
Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice
McManus, R. M., Higgins, S. C., Mills, K. H. G., & Lynch, M. A. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.07.025 · Cited by 132 · see citing works
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Direct Visualization of Fungal Infection in Brains from Patients with Alzheimer's Disease
Pisa, D., Alonso, R., Juarranz, Á., Rábano, A., & Carrasco, L. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141386 · Cited by 111 · see citing works
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Roodveldt, C., Labrador‐Garrido, A., González‐Rey, E., Lachaud, C. C., Guilliams, T., Fernández-Montesinos, R., Benitez-Rondan, A., Robledo, G., Hmadcha, A., Delgado, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079160 · Cited by 96 · see citing works
Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., & Petrasek, T. (2022) · PLOS Pathogens · doi:10.1371/journal.ppat.1010929 · Cited by 92 · see citing works
Percy, M. E., Kruck, T. P. A., Pogue, A. I., & Lukiw, W. J. (2011) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.08.001 · Cited by 88 · see citing works
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Tarawneh, R. M., & Penhos, E. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104814 · Cited by 89 · see citing works
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Balin, B. J., Hammond, C. J., Little, C. S., Hingley, S. T., Al-Atrache, Z., Appelt, D. M., Whittum-Hudson, J. A., & Hudson, A. P. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00302 · Cited by 77 · see citing works
Self-citationCarter, C. (2017) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-170017 · Cited by 70 · see citing works
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Nagu, P., Parashar, A., Behl, T., & Mehta, V. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01829-3 · Cited by 64 · see citing works
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Chacko, A., Delbaz, A., Walkden, H., Basu, S., Armitage, C. W., Eindorf, T., Trim, L. K., Miller, E., West, N. P., St John, J. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06749-9 · Cited by 65 · see citing works
Novel targets in Alzheimer’s disease: A special focus on microglia
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Kell, D. B., Potgieter, M., & Pretorius, E. (2015) · F1000Research · doi:10.12688/f1000research.6709.2 · Cited by 58 · see citing works
Lynch, M. A. (2014) · Immunology · doi:10.1111/imm.12156 · Cited by 64 · see citing works
Periodontitis: a potential risk factor for Alzheimer's disease
Cerajewska, T., Davies, M., & West, N. (2015) · BDJ · doi:10.1038/sj.bdj.2014.1137 · Cited by 71 · see citing works
Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development
Patel, A. L., Chen, X., Wood, S. T., Stuart, E. S., Arcaro, K. F., Molina, D. P., Petrović, S., Furdui, C. M., & Tsang, A. W. (2014) · BMC Microbiology · doi:10.1186/s12866-014-0277-4 · Cited by 56 · see citing works
Pretorius, E., Bester, J., & Kell, D. B. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160318 · Cited by 59 · see citing works
The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease
Iqbal, U., Zeng, E., & Pasinetti, G. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144920 · Cited by 55 · see citing works
Clinical and Preclinical Studies of Fermented Foods and Their Effects on Alzheimer’s Disease
Kumar, M. R., Azizi, N. F., Yeap, S. K., Abdullah, J. O., Khalid, M., Omar, A. R., Osman, M. A., Leow, T. C., Mortadza, S. A. S., & Alitheen, N. B. (2022) · Antioxidants · doi:10.3390/antiox11050883 · Cited by 53 · see citing works
Foroughi, M. R., Torabinejad, M., Angelov, N., Ojcius, D. M., Parang, K., Ravnan, M. C., & Lam, J. T. (2025) · Infection · doi:10.1007/s15010-025-02568-y · Cited by 53 · see citing works
Tang, Z., Liang, D., Cheng, M., Su, X., Liu, R., Zhang, Y., & Wu, H. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01629-1 · Cited by 53 · see citing works
Infectious burden and cognitive decline in the northern Manhattan study
Wright, C. B., Gardener, H., Dong, C., Yoshita, M., DeCarli, C., Sacco, R. L., Stern, Y., & Elkind, M. S. V. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13557 · Cited by 52 · see citing works
Wang, J., Ye, F., Cheng, X., Zhang, X., Liu, F., Liu, G., Ni, M., Qiao, S., Zhou, W., & Zhang, Y. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160138 · Cited by 52 · see citing works
Exploring pathological link between antimicrobial and amyloid peptides
Tang, Y., Zhang, Y., Zhang, D., Liu, Y., Nussinov, R., & Zheng, J. (2024) · Chemical Society Reviews · doi:10.1039/d3cs00878a · Cited by 50 · see citing works
Pietro, M. D., Filardo, S., Romano, S., & Sessa, R. (2019) · Microorganisms · doi:10.3390/microorganisms7050140 · Cited by 51 · see citing works
Carter, C. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/140539 · Cited by 46 · see citing works
Lim, C., Hammond, C. J., Hingley, S. T., & Balin, B. J. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0217-0 · Cited by 45 · see citing works
Self-citationCarter, C. J. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.003 · Cited by 44 · see citing works
Dhami, M., Raj, K., & Singh, S. (2023) · Aging and Health Research · doi:10.1016/j.ahr.2023.100128 · Cited by 42 · see citing works
Shim, S.-M., Cheon, H., Jo, C., Koh, Y. H., Song, J., & Jeon, J. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160563 · Cited by 40 · see citing works
Salin, O., Törmäkangas, L., Leinonen, M., Saario, E., Hagström, M., Ketola, R. A., Saikku, P., Vuorela, H. J., & Vuorela, P. M. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf2032473 · Cited by 40 · see citing works
Al-Atrache, Z., Lopez, D. B., Hingley, S. T., & Appelt, D. M. (2019) · BMC Neuroscience · doi:10.1186/s12868-019-0489-5 · Cited by 37 · see citing works
Self-citationSchlegel, P., Novotný, M., Klímová, B., & Vališ, M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190460 · Cited by 38 · see citing works
Bocharova, O. V., Pandit, N. P., Molesworth, K., Fisher, A., Mychko, O., Makarava, N., & Baskakov, I. V. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100845 · Cited by 34 · see citing works
Joshi, Y. B., Giannopoulos, P. F., Chu, J., & Praticò, D. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.016 · Cited by 29 · see citing works
The Viral Hypothesis in Alzheimer’s Disease: Novel Insights and Pathogen-Based Biomarkers
Naughton, S. X., Raval, U., & Pasinetti, G. M. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030074 · Cited by 30 · see citing works
A 16S rRNA gene sequencing based study of oral microbiota in migraine patients in China
Jiang, W., Wang, T., Liu, C., Deng, M., Ren, X., Wang, F., Zhang, Y., Yu, X., Yao, L., & Wang, Y. (2021) · Bioengineered · doi:10.1080/21655979.2021.1933840 · Cited by 25 · see citing works
Alzheimer's disease – the ‘microbial hypothesis’ from a clinical and neuroimaging perspective
Frölich, L. (2020) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2020.111181 · Cited by 24 · see citing works
Woods, J. J., Skelding, K. A., Martin, K. L., Aryal, R., Sontag, E., Johnstone, D. M., Horvat, J. C., Hansbro, P. M., & Milward, E. A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.10.014 · Cited by 23 · see citing works
An agent-based model to investigate microbial initiation of Alzheimer’s via the olfactory system
Sundar, S., Battistoni, C., McNulty, R., Morales, F., Gorky, J. M., Foley, H. C., & Dhurjati, P. (2020) · Theoretical Biology and Medical Modelling · doi:10.1186/s12976-020-00123-w · Cited by 23 · see citing works
Rubin, K., & Glazer, S. (2016) · Immunobiology · doi:10.1016/j.imbio.2016.09.017 · Cited by 23 · see citing works
Cheok, Y. Y., Lee, C. Y. Q., Cheong, H. C., Looi, C. Y., & Wong, W. F. (2020) · Microorganisms · doi:10.3390/microorganisms8010127 · Cited by 23 · see citing works
Microbiome influences on neuro-immune interactions in neurodegenerative disease
Menees, K. B., Otero, B. A., & Tansey, M. G. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.07.006 · Cited by 23 · see citing works
Chlamydia pneumoniae in Alzheimer's disease pathology
Subedi, L., Gaire, B. P., Koronyo, Y., Koronyo‐Hamaoui, M., & Crother, T. R. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1393293 · Cited by 23 · see citing works
Walkden, H., Delbaz, A., Nazareth, L., Batzloff, M., Shelper, T., Beacham, I. R., Chacko, A., Shah, M., Beagley, K. W., Tello Velasquez, J., et al. (2020) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0008017 · Cited by 21 · see citing works
Khoshbayan, A., Taheri, F., Moghadam, M. T., Chegini, Z., & Shariati, A. (2021) · Microbial Pathogenesis · doi:10.1016/j.micpath.2021.104803 · Cited by 20 · see citing works
Systemic Inflammation Causes Microglial Dysfunction With a Vascular AD phenotype
Bathini, P., Dupanloup, I., Zenaro, E., Terrabuio, E., Fischer, A., Ballabani, E., Doucey, M., & Alberi, L. A. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100568 · Cited by 20 · see citing works
Tang, Y., Zhang, D., Gong, X., & Zheng, J. (2022) · Chemical Science · doi:10.1039/d2sc01447e · Cited by 19 · see citing works
Ou, H., Chien, W., Chung, C., Chang, H., Kao, Y., Wu, P.-C., & Tzeng, N. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.701899 · Cited by 17 · see citing works
Exploring the Mechanisms and Association between Oral Microflora and Systemic Diseases
Issrani, R., Reddy, J., El‐Metwally, T. H., Prabhu, N., Alruwaili, M. K., Munisekhar, M. S., Alshammari, S. M., & Alghumaiz, S. F. (2022) · Diagnostics · doi:10.3390/diagnostics12112800 · Cited by 19 · see citing works
Gaire, B. P., Koronyo, Y., Vit, J., Hutton, A., Subedi, L., Fuchs, D.-T. S., Swerdlow, N., Rentsendorj, A., Shahin, S., Martinon, D., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68580-4 · Cited by 16 · see citing works
Zhan, X., Hakoupian, M., Jin, L., & Sharp, F. R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.705594 · Cited by 16 · see citing works
The study of memory and executive dysfunction in patients infected with Helicobacter pylori
Rezvani, F., Sayadnasiri, M., & Rezaei, O. (2017) · Neurological Research · doi:10.1080/01616412.2017.1363349 · Cited by 15 · see citing works
Evidence for horizontal gene transfer betweenChlamydophila pneumoniaeand Chlamydia phage
Rosenwald, A., Murray, B., Toth, T., Madupu, R., Kyrillos, A., & Arora, G. S. (2014) · Bacteriophage · doi:10.4161/21597073.2014.965076 · Cited by 15 · see citing works
Role of Chlamydia pneumoniae in community-acquired pneumonia in hospitalized Jordanian adults
Al-Aydie, S. N., Obeidat, N. M., & Al‐Younes, H. M. (2016) · The Journal of Infection in Developing Countries · doi:10.3855/jidc.6590 · Cited by 14 · see citing works
Roberts, J. A., Elkind, M. S. V., Liu, M., Wright, C. B., Rundek, T., & Gutierrez, J. (2023) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2023.120856 · Cited by 13 · see citing works
A reappraisal on amyloid cascade hypothesis: The role of chronic infection in Alzheimer’s disease
Phuna, Z. X., & Madhavan, P. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2045290 · Cited by 12 · see citing works
Does Dementia Have a Microbial Cause?
Landry, R. L., & Embers, M. E. (2022) · NeuroSci · doi:10.3390/neurosci3020019 · Cited by 12 · see citing works
Nicolson, G. L., Settineri, R. A., & Ellithorpe, R. R. (2014) · Functional Foods in Health and Disease · doi:10.31989/ffhd.v4i1.26 · Cited by 13 · see citing works
Periodontitis: a potential risk factor for Alzheimer's disease
Cerajewska, T. L., Davies, M., & West, N. X. (2016) · BDJ Team · doi:10.1038/bdjteam.2016.62 · Cited by 12 · see citing works
Renegade cellular and bacterial genetic sequences in monkey-derived stealth adapted viruses
Wj, M. (2019) · Journal of Human Virology & Retrovirology · doi:10.15406/jhvrv.2019.07.00211 · Cited by 11 · see citing works
Nazareth, L., Walkden, H., Chacko, A., Delbaz, A., Shelper, T., Armitage, C. W., Reshamwala, R., Trim, L. K., St John, J. A., Beagley, K. W., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.607779 · Cited by 12 · see citing works
Underly, R. G., Song, M.-S., Dunbar, G. L., & Weaver, C. L. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00259 · Cited by 11 · see citing works
Feed your microbiome and improve sleep, stress resilience, and cognition
Chichlowski, M., Cotter, J., Fawkes, N., & Pandey, N. (2022) · Exploration of Medicine · doi:10.37349/emed.2022.00097 · Cited by 10 · see citing works
Shah, A., Morris, J. A., & Wray, M. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.110035 · Cited by 10 · see citing works
Norins, L. C. (2021) · Antibiotics · doi:10.3390/antibiotics10030327 · Cited by 9 · see citing works
Amyloid and Tau Protein Concentrations in Children with Meningitis and Encephalitis
Sulik, A., Toczyłowski, K., Kulczyńska‐Przybik, A., & Mroczko, B. (2022) · Viruses · doi:10.3390/v14040725 · Cited by 9 · see citing works
Ni, J., & Wu, Z. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.638686 · Cited by 9 · see citing works
Carter, C. J. (2011) · ISRN Neurology · doi:10.5402/2011/394678 · Cited by 9 · see citing works
Parker, A., James, S. A., Purse, C., Brion, A., Goldson, A. J., Telatin, A., Baker, D., & Carding, S. R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.828429 · Cited by 8 · see citing works
Viruses Disguised as Self and/or as Bacteria
Martin, W. J. (2020) · Microbiology & Infectious Diseases · doi:10.33425/2639-9458.1076 · Cited by 8 · see citing works
Armitage, C. W., O'Meara, C. P., & Beagley, K. W. (2015) · Scandinavian Journal of Immunology · doi:10.1111/sji.12295 · Cited by 8 · see citing works
Role of Microbiota in Neurodegenerative Diseases
Sobol, C. V. (2018) · Russian Journal of Developmental Biology · doi:10.1134/s1062360418060061 · Cited by 7 · see citing works
Roberts, J. A., Elkind, M. S. V., Liu, M., Assuras, S., Levin, B. E., Guzmán, V., Rundek, T., & Gutierrez, J. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70457 · Cited by 6 · see citing works
The oral - X axis: from periodontal dysbiosis to systemic disease
Jin, W., Tang, L., Yang, J., Hu, X., Guo, W., Ai, H., Zuo, Y., & Jin, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1806445 · Cited by 7 · see citing works
- Authors
- Hammond, C. J., Hallock, L. R., Howanski, R. J., Appelt, D. M., Little, C. S., & Balin, B. J.
- Affiliations
- Philadelphia College of Osteopathic Medicine (US)
- Corresponding author
- Balin, Brian J
- Venue
- BMC Neuroscience
- Published
- 2010-09-23
- Volume
- 11
- Issue
- 1
- Pages
- 121-121
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC2949767
- OpenAlex
- W2056188402
- Cited by
- 156
- References
- 49
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 6 · 2023: 4 · 2022: 21 · 2021: 12 · 2020: 17 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 12 · 2015: 7 · 2014: 11 · 2013: 11 · 2012: 4
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Drexel University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Chlamydia pneumoniae, Alzheimer's disease, late-onset Alzheimer's disease, chlamydia, amyloid plaques, amyloid-beta, neurofibrillary tangles, frontal and temporal cortex, antibody specificity, neuroinflammation, Alzheimer's disease pathogenesis
- MeSH terms
- Aged, Alzheimer Disease, Brain, Brain Chemistry, Cerebral Cortex, Chlamydia Infections, Coloring Agents, Female, Humans, Immunohistochemistry, Male, Thiazoles, Tissue Banks, Reproducibility of Results, Amyloid beta-Peptides, Neurofibrillary Tangles, Chlamydophila pneumoniae, Benzothiazoles, Plaque, Amyloid
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