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Elgh, Fredrik
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Publications (10 of 92) Show all publications
Egorova, O., Myte, R., Schneede, J., Hägglöf, B., Bölte, S., Domellöf, E., . . . Silfverdal, S.-A. (2020). Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers. Molecular Autism, 11, Article ID 7.
Open this publication in new window or tab >>Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
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2020 (English)In: Molecular Autism, ISSN 2040-2392, Vol. 11, article id 7Article in journal (Refereed) Published
Abstract [en]

Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.

Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.

Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22–2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.

Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Autism, Pregnancy, One-carbon metabolism, Folate, Vitamin B, Vitamin D, Vitamin A, Inflammation
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:umu:diva-167467 (URN)10.1186/s13229-020-0315-z (DOI)
Available from: 2020-01-22 Created: 2020-01-22 Last updated: 2020-01-23Bibliographically approved
Lopatko Lindman, K., Weidung, B., Olsson, J., Josefsson, M., Kok, E., Johansson, A., . . . Lövheim, H. (2019). A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated Alzheimer's disease. Alzheimer's & dementia, 5, 697-704
Open this publication in new window or tab >>A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated Alzheimer's disease
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2019 (English)In: Alzheimer's & dementia, ISSN 1552-5279, Vol. 5, p. 697-704Article in journal (Refereed) Published
Abstract [en]

Introduction: Herpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis.

Methods: Plasma from 360 AD cases, obtained on average 9.6 years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland.

Results: The interaction between APOEε4 heterozygosity (APOEε24 or ε3/ε4) and anti-HSV1 IgG carriage increased the risk of AD (OR 4.55, P = .02). A genetic risk score based on the nine AD risk genes also interacted with anti-HSV1 IgG for the risk of developing AD (OR 2.35, P = .01).

Discussion: The present findings suggest that the APOEε4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

Keywords
APOEε4, Alzheimer's disease, Apolipoprotein E4, Dementia, HSV, Herpes simplex, Nested case-control study
National Category
Clinical Medicine
Research subject
Medical Virology
Identifiers
urn:nbn:se:umu:diva-167226 (URN)10.1016/j.trci.2019.09.014 (DOI)31921962 (PubMedID)
Available from: 2020-01-13 Created: 2020-01-13 Last updated: 2020-01-14Bibliographically approved
Lövheim, H., Norman, T., Weidung, B., Olsson, J., Josefsson, M., Adolfsson, R., . . . Elgh, F. (2019). Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study. Journal of Alzheimer's Disease, 67(1), 211-220
Open this publication in new window or tab >>Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed) Published
Abstract [en]

Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer’s disease, APOE ɛ4, apolipoprotein E4, cognitive impairment, cohort study, dementia, epidemiological study, episodic memory, herpes simplex virus
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162728 (URN)10.3233/JAD-171162 (DOI)000457778000017 ()30636735 (PubMedID)
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-09-10Bibliographically approved
Olsson, J., Johansson, J., Honkala, E., Blomqvist, B., Kok, E., Weidung, B., . . . Elgh, F. (2019). Urea dilution of serum for reproducible anti-HSV1 IgG avidity index. BMC Infectious Diseases, 19, Article ID 164.
Open this publication in new window or tab >>Urea dilution of serum for reproducible anti-HSV1 IgG avidity index
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2019 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, article id 164Article in journal (Refereed) Published
Abstract [en]

Herpes simplex virus type 1 (HSV1), establishes life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe a protocol to generate a reliable and discriminative avidity index (AI) for anti-HSV1 IgG content in human sera. Human serum from two distinct cohorts; one a biobank collection (Betula) (n = 28), and one from a clinical diagnostics laboratory at Northern Sweden University Hospital (NUS) (n = 18), were assessed for presence of IgG antibodies against HSV1 by a commercially available ELISA-kit. Addition of urea at the incubation step reduces effective binding, and the ratio between urea treated sample and non-treated sample was used to express an avidity index (AI) for individual samples. AI score ranged between 43.2 and 73.4% among anti-HSV1 positive biobank sera. Clinical samples ranged between 36.3 and 74.9%. Reproducibility expressed as an intraclass correlation coefficient (ICC) was estimated at 0.948 (95% CI: 0.900-0.979) and 0.989 (95% CI 0.969-0.996) in the biobank and clinical samples, respectively. The method allows for AI scoring of anti-HSV1 IgG from individual human sera with a single measurement. The least significant change between two measurements at the p < 0.05 level was estimated at 5.4 and 3.2 points, respectively, for the two assessed cohorts.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Herpes simplex, IgG, Avidity, ELISA, Primary infection, Reactivated infection
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-157213 (URN)10.1186/s12879-019-3769-x (DOI)000459030400003 ()30764767 (PubMedID)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Kinsman, J., Stöven, S., Elgh, F., Murillo, P. & Sulzner, M. (2018). Good practices and challenges in addressing poliomyelitis and measles in the European Union. European Journal of Public Health, 28(4), 730-734
Open this publication in new window or tab >>Good practices and challenges in addressing poliomyelitis and measles in the European Union
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2018 (English)In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 28, no 4, p. 730-734Article in journal (Refereed) Published
Abstract [en]

Background: All European Union (EU) and European Economic Area (EEA) Member States have pledged to ensure political commitment towards sustaining the region's poliomyelitis-free status and eliminating measles. However, there remain significant gaps between policy and practice in many countries. This article reports on an assessment conducted for the European Commission that aimed to support improvements in preparedness and response to poliomyelitis and measles in Europe.

Methods: A documentary review was complemented by qualitative interviews with professionals working in International and EU agencies, and in at-risk or recently affected EU/EEA Member States (six each for poliomyelitis and measles). Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data were subjected to thematic analysis. Preliminary findings were then discussed at a Consensus Workshop with 22 of the interviewees and eight other experts.

Results: Generic or disease-specific plans exist in the participating countries and cross-border communications during outbreaks were generally reported as satisfactory. However, surveillance systems are of uneven quality, and clinical expertise for the two diseases is limited by a lack of experience. Serious breaches of protocol have recently been reported from companies producing poliomyelitis vaccines, and vaccine coverage rates for both diseases were also sub-optimal. A set of suggested good practices to address these and other challenges is presented.

Conclusions: Poliomyelitis and measles should be brought fully onto the policy agendas of all EU/EEA Member States, and adequate resources provided to address them. Each country must abide by the relevant commitments that they have already made.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-150590 (URN)10.1093/eurpub/cky056 (DOI)000440944400026 ()29659793 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-09-11Bibliographically 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
Stenberg, P. (2018). Pehr Stenbergs levernesbeskrivning: av honom själv författad på dess lediga stunder. D.5, register. Umeå: Forskningsarkivet vid Umeå universitet
Open this publication in new window or tab >>Pehr Stenbergs levernesbeskrivning: av honom själv författad på dess lediga stunder. D.5, register
2018 (Swedish)Book (Other academic)
Place, publisher, year, edition, pages
Umeå: Forskningsarkivet vid Umeå universitet, 2018. p. 140
Series
Urkunden: källserie utgiven av Forskningsarkivet vid Umeå universitet, ISSN 0284-2734 ; 23
Keywords
Stenberg, Pehr, 1758-1824, Präster, Sverige. 1700-talet, Biografi
National Category
Other Humanities not elsewhere specified
Identifiers
urn:nbn:se:umu:diva-146077 (URN)978-91-7601-112-6 (ISBN)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2019-05-09Bibliographically approved
Kinsman, J., Angrén, J., Elgh, F., Furberg, M., Mosquera, P. A., Otero-García, L., . . . Tsolova, S. (2018). Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states. BMC Health Services Research, 18(1), Article ID 528.
Open this publication in new window or tab >>Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states
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2018 (English)In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, no 1, article id 528Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus).

METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration.

RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State.

CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Cross-border, European Union, Inter-sectoral, Interoperability, MERS-coronavirus, Poliomyelitis, Preparedness and response, Public health, Risk communication
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-150589 (URN)10.1186/s12913-018-3326-0 (DOI)000437989700001 ()29976185 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-16Bibliographically approved
Olsson, J., Kok, E., Adolfsson, R., Lövheim, H. & Elgh, F. (2017). Herpes virus seroepidemiology in the adult Swedish population. Immunity & Ageing, 14, Article ID 10.
Open this publication in new window or tab >>Herpes virus seroepidemiology in the adult Swedish population
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2017 (English)In: Immunity & Ageing, ISSN 1742-4933, E-ISSN 1742-4933, Vol. 14, article id 10Article in journal (Refereed) Published
Abstract [en]

Background: Herpes viruses establish a life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1), Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV) and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years of age). Methods: Presence of antibodies against the respective viruses in serum from individuals in the Betula study was determined with an enzyme-linked immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the five HHVs mentioned above. In addition, samples including follow-up samples collected 1988-2010 from 3,444 persons were analyzed for HSV. Results: Prevalence of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus infections were more common among women (p = 0.010) and a lower age-adjusted HSV seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence of HSV infection was estimated at 14.0/1000. Conclusion: Women are more often seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was lower in later birth cohorts indicating a decreasing childhood and adolescent risk of infection.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Herpes, Herpes simplex, Cytomegalovirus, Varicella zoster virus, Seroprevalence, Epidemiology
National Category
Geriatrics Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-136062 (URN)10.1186/s12979-017-0093-4 (DOI)000401191100001 ()28491117 (PubMedID)
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-06-09Bibliographically approved
Lövheim, H., Elgh, F., Johansson, A., Zetterberg, H., Blennow, K., Hallmans, G. & Eriksson, S. (2017). Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease. Alzheimer's & Dementia, 13(7), 778-782
Open this publication in new window or tab >>Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease
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2017 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 7, p. 778-782Article in journal (Refereed) Published
Abstract [en]

Introduction: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)—central in the pathogenesis of AD—is a logical candidate, but studies to date have produced conflicting results on its utility.

Methods: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNO-BIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42.

Results: Plasma concentrations of free Aβ40 and Aβ42 did not differ between preclinical AD cases and dementia-free controls, in the full sample or in subgroups defined according to sex and age group (<60 and ≥ 60 years). The interval between sampling and AD diagnosis did not affect the results. Aβ concentrations did not change in the years preceding AD diagnosis among individuals for whom longitudinal samples were available.

Discussion: Plasma concentrations of free Aβ could not predict the development of clinical AD, and Aβ concentrations did not change in the years preceding AD diagnosis in this sample. These results indicate that free plasma Aβ is not a useful biomarker for the identification of individuals at risk of developing clinical AD.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Plasma amyloid β, Aβ, Alzheimer's disease, Dementia, Preclinical Alzheimer's disease, Biomarker
National Category
Neurology
Research subject
Geriatrics
Identifiers
urn:nbn:se:umu:diva-126471 (URN)10.1016/j.jalz.2016.12.004 (DOI)000404559300006 ()
Available from: 2016-10-07 Created: 2016-10-07 Last updated: 2018-08-31Bibliographically approved
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