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Jensen, A. B., Haubek, D., Claesson, R., Johansson, A. & Nørskov-Lauritsen, N. (2019). Comprehensive antimicrobial susceptibility testing of a large collection of clinical strains of Aggregatibacter actinomycetemcomitans does not identify resistance to amoxicillin. Journal of Clinical Periodontology, 46(8), 846-854
Open this publication in new window or tab >>Comprehensive antimicrobial susceptibility testing of a large collection of clinical strains of Aggregatibacter actinomycetemcomitans does not identify resistance to amoxicillin
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2019 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 46, no 8, p. 846-854Article in journal (Refereed) Published
Abstract [en]

AIM: The present study aims to determine the susceptibility of Aggregatibacter actinomycetemcomitans to amoxicillin by investigating a large collection of oral strains of diverse geographical origin.

METHODS: Two hundred and fifty-seven A. actinomycetemcomitans strains were serotyped using a multiplex polymerase chain reaction, and minimal inhibitory concentration (MIC) values of amoxicillin were determined using the agar dilution method (range 0.25 to 8.0 mg/L). The plates were spot-wise inoculated with approximately 104 colony-forming units, incubated in 5% CO2 at 37 C°, and visually inspected after 24 and 48 hours. A MIC ≤ 2.00 mg/L was categorised as susceptible using EUCAST interpretative criteria for Haemophilus species.

RESULTS: Amoxicillin MIC-values varied from 0.25 mg/L to 2.00 mg/L, and all tested strains, including strains previously reported as resistant, were susceptible to amoxicillin. The MIC50 was 1.00 mg/L and the MIC90 was 2.00 mg/L.

CONCLUSION: Meticulous investigation of strains including isolates previously reported as resistant could not confirm the emergence of resistance to β-lactams in A. actinomycetemcomitans. Based on the present in vitro results, amoxicillin can be considered a key oral antimicrobial agent for treatment of A. actinomycetemcomitans. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
EUCAST, Antimicrobial resistance, agar dilution method, breakpoints, β-lactams
National Category
Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-159488 (URN)10.1111/jcpe.13148 (DOI)000476508700007 ()31124155 (PubMedID)2-s2.0-85068110794 (Scopus ID)
Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-08-12Bibliographically approved
Johansson, A., Claesson, R., Höglund-Åberg, C., Haubek, D., Lindholm, M., Jasim, S. & Oscarsson, J. (2019). Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden. Pathogens, 8(3), 1-13, Article ID 153.
Open this publication in new window or tab >>Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 3, p. 1-13, article id 153Article in journal (Refereed) Published
Abstract [en]

The bacterium Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis and with systemic diseases, such as endocarditis. By assessing a Ghanaian longitudinal adolescent cohort, we earlier recognized the cagE gene as a possible diagnostic marker for a subgroup of JP2 and non-JP2 genotype serotype b A. actinomycetemcomitans strains, associated with high leukotoxicity as determined in a semi-quantitative cell assay. This group of A. actinomycetemcomitans is associated with the progression of attachment loss. In the present work, we used conventional polymerase chain reaction (PCR) and quantitative PCR to perform the cagE genotyping of our collection of 116 selected serotype b A. actinomycetemcomitans strains, collected over a period of 15 years from periodontitis patients living in Sweden. The A. actinomycetemcomitans strains carrying cagE (referred to as cagE+; n = 49) were compared to the cagE-negative strains (n = 67), present at larger proportions in the subgingival plaque samples, and were also much more prevalent in the young (≤35 years) compared to in the old (>35 years) group of patients. Our present results underline the potential use of cagE genotyping in the risk assessment of the development of periodontal attachment loss in Swedish adolescents.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans; cagE; virB1; virB4; genotype; virulence
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-163485 (URN)10.3390/pathogens8030153 (DOI)31533208 (PubMedID)
Available from: 2019-09-23 Created: 2019-09-23 Last updated: 2019-09-25Bibliographically approved
Pietiäinen, M., Liljestrand, J. M., Akhi, R., Buhlin, K., Johansson, A., Paju, S., . . . Pussinen, P. J. (2019). Saliva and Serum Immune Responses in Apical Periodontitis. Journal of clinical medicine, 8(6), Article ID 889.
Open this publication in new window or tab >>Saliva and Serum Immune Responses in Apical Periodontitis
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2019 (English)In: Journal of clinical medicine, ISSN 2077-0383, Vol. 8, no 6, article id 889Article in journal (Refereed) Published
Abstract [en]

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01-8.33) and 4.91 (2.48-9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48-2.97)), serum IgG to bacterial antigens (4.66 (1.22-10.1)), and Gram-negative subgingival species (1.98 (1.16-3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05-21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis-a putative risk factor for systemic diseases.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
adaptive immunity, antibody, apical periodontitis, saliva, serum
National Category
Clinical Medicine
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-161062 (URN)10.3390/jcm8060889 (DOI)000475349300133 ()31234349 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-08-12Bibliographically approved
Pettersson, M., Pettersson, J., Johansson, A. & Molin Thorén, M. (2019). Titanium release in peri-implantitis. Journal of Oral Rehabilitation, 46(2), 179-188
Open this publication in new window or tab >>Titanium release in peri-implantitis
2019 (English)In: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842, Vol. 46, no 2, p. 179-188Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or periodontitis and to examine whether Ti particles can be identified in samples from peri-implantitis lesions.

Background: Long-term follow-up studies show that implant usage to replace missing or lost teeth is a safe and predictable treatment. However, inflammation and loss of supporting bone around an implant (peri-implantitis) lead to patient suffering and costs. Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis tissue is unknown.

Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analyzed with inductively coupled plasma mass spectrometry (ICP-MS) for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analyzed microscopically with light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) with element analysis to investigate the presence of particulate Ti.

Results: All patients lost one or more implants despite undergoing peri-implant or periodontal treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than periodontitis tissue with a mean ± SDof 98.7 ± 85.6 μg/g and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and periodontitis biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue. The mean size ± SDof the visible particles with LM was 10.9 ± 35.7 μm2 (mean of three repeated measurements) (95% CI, 6.5-15.3).

Conclusion: We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
energy dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, light microscopy, peri-implantitis, scanning electron microscopy, titanium
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-147118 (URN)10.1111/joor.12735 (DOI)000455483300010 ()30325523 (PubMedID)
Funder
Västerbotten County Council, VLL 1147-2014
Note

Originally included in thesis in manuscript form.

Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2019-02-08Bibliographically approved
Oscarsson, J., Claesson, R., Lindholm, M., Höglund-Åberg, C. & Johansson, A. (2019). Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response. Journal of Clinical Medicine, 8(7), Article ID 1079.
Open this publication in new window or tab >>Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response
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2019 (English)In: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, no 7, article id 1079Article in journal (Refereed) Published
Abstract [en]

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases.

Place, publisher, year, edition, pages
Basel: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans, cytolethal distending toxin, invasiveness, leukotoxin, outer membrane vesicles, serum resistance
National Category
Medical Biotechnology
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-161754 (URN)10.3390/jcm8071079 (DOI)31336649 (PubMedID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-29Bibliographically approved
Perez-Cornago, A., Appleby, P. N., Boeing, H., Gil, L., Kyrø, C., Ricceri, F., . . . Travis, R. C. (2018). Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls. International Journal of Cancer, 143(11), 2677-2686
Open this publication in new window or tab >>Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 11, p. 2677-2686Article in journal (Refereed) Published
Abstract [en]

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between pre-diagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs Q1=0.61, 95% confidence interval [CI]=0.39-0.97), although there was no significant trend (OR per 75 percentile increase=0.69, 95 CI=0.46-1.05, Ptrend =0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs Q1=0.70, 0.45-1.10, and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that pre-diagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
isoflavones, lignans, phytoestrogens, pooled analysis, prostate cancer risk
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150143 (URN)10.1002/ijc.31640 (DOI)000450846900006 ()29971774 (PubMedID)2-s2.0-85054090054 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2018-07-10 Created: 2018-07-10 Last updated: 2018-12-19Bibliographically approved
Boles, U., Johansson, A., Wiklund, U., Sharif, Z., David, S., McGrory, S. & Henein, M. Y. (2018). Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis. International Journal of Molecular Sciences, 19(1), Article ID 260.
Open this publication in new window or tab >>Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis
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2018 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 1, article id 260Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2018
Keywords
atherosclerosis, coronary artery disease, coronary artery ectasia, cytokines, immune inflammatory response, macrophage activation
National Category
Cardiac and Cardiovascular Systems
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-144041 (URN)10.3390/ijms19010260 (DOI)000424407200254 ()29337902 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2019-09-23Bibliographically approved
Pettersson, M., Pettersson, J., Molin Thorén, M. & Johansson, A. (2018). Effect of cobalt ions on the interaction between macrophages and titanium. Journal of Biomedical Materials Research. Part A (9), 2518-2530
Open this publication in new window or tab >>Effect of cobalt ions on the interaction between macrophages and titanium
2018 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, no 9, p. 2518-2530Article in journal (Refereed) Published
Abstract [en]

Inflammation and bone reduction around dental implants are described as periimplantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL-1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro-inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP-1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL-1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy (ICP-AES) and electron microscopy. Co at a concentration of 100 μM neutralized the IL-1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti-induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti-induced activation and release of active IL-1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal-protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localization after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri-implant tissue.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
titanium, cobalt, interleukin-1β, peri-implantitis, aggregate formation
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-147124 (URN)10.1002/jbm.a.36447 (DOI)000445615600016 ()29708655 (PubMedID)
Funder
Västerbotten County Council, VLL 1147-2014
Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2018-12-05Bibliographically approved
Engström, M., Eriksson, K., Lee, L., Hermansson, M., Johansson, A., Nicholas, A. P., . . . Yucel-Lindberg, T. (2018). Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis. Journal of Translational Medicine, 16, Article ID 214.
Open this publication in new window or tab >>Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis
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2018 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 16, article id 214Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases (PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), producing leukotoxin as virulence factor. These two oral bacteria have been suggested to be linked to anti-citrullinated protein antibodies in patients with RA.

METHODS: Gingival tissue biopsies were obtained from 15 patients with periodontitis and 15 individuals without periodontal disease. Presence of CD3-positive lymphocytes, citrullinated proteins, PAD2, PAD4, P. gingivalis as well as A. actinomycetemcomitans and Mannheimia haemolytica produced leukotoxins were analysed by immunohistochemistry, followed by triple-blind semi-quantitative analysis. Mann-Whitney and Fisher's exact tests were used to analyse differences between groups. PADI2 and PADI4 mRNA levels were assessed by RT-qPCR and analysed using Wilcoxon signed rank test.

RESULTS: Increased staining of citrullinated proteins was observed in gingival connective tissue from subjects with periodontitis (80%, 12/15) compared to healthy gingival tissue (27%, 4/15), whereas no differences were observed in gingival epithelium. There was also an increased staining of the citrullinating enzymes PAD2 and PAD4 in gingival connective tissue of patients with periodontitis whereas similar levels of PAD2 and PAD4 were observed in the gingival epithelium of the two groups. Similarly, the mRNA levels of PADI2 and PADI4 were also increased in the gingival tissue of patients with periodontitis compared to healthy controls. Furthermore, presence of P. gingivalis and leukotoxins was comparable in both epithelium and connective tissue, from the different investigated individuals with and without periodontitis, and there were no correlations between the presence of periodontal pathogens and the expression of citrullinated proteins or PAD enzymes.

CONCLUSION: Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. The increased citrullination and PAD2 and PAD4 expression in periodontitis were, however, independent of the presence of periodontal pathogen P. gingivalis and A. actinomycetemcomitans leukotoxin.

Keywords
Aggregatibacter actinomycetemcomitans, Citrullinated proteins, Gingival tissue, Inflammation, Leukotoxin, Peptidylarginine deiminases, Periodontitis, Porphyromonas gingivalis
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-150297 (URN)10.1186/s12967-018-1588-2 (DOI)000440362700002 ()30064459 (PubMedID)2-s2.0-85050781410 (Scopus ID)
Available from: 2018-08-03 Created: 2018-08-03 Last updated: 2018-11-01Bibliographically approved
Lövheim, H., Olsson, J., Weidung, B., Johansson, A., Eriksson, S., Hallmans, G. & Elgh, F. (2018). Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development. Journal of Alzheimer's Disease, 61, 939-945
Open this publication in new window or tab >>Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development
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2018 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, p. 939-945Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies.

OBJECTIVE: To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.

METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses.

RESULTS: The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007).

CONCLUSION: The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

Keywords
Alzheimer’s disease, Herpes simplex virus, cytomegalovirus, dementia, nested case-control study
National Category
Medical and Health Sciences
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-143394 (URN)10.3233/JAD-161305 (DOI)000422845200010 ()29254081 (PubMedID)
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-08-31Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8069-8263

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