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.
To ...investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.
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.
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).
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.
Abstract 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.
The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular ...composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
•Storage time explains up to 35 % of plasma protein concentration variation in frozen biobank samples from healthy women.•Storage time exert similar effect sizes as individual age and should be included as a covariate in epidemiological studies.
One basic requirement of life science research is the quality of samples. Proper handling and rigorous biobanking of clinical samples is crucial for collection of samples for rare diseases, for monitoring individual variation in longitudinal studies and for prospective studies of biomarkers and risk of developing for instance cardiovascular disease. We have studied the effect of long-time storage, individual age and sampling month and conclude that storage-time has similar impact on protein levels as age. The results emphasize the need to include sample parameters as covariates in future epidemiological studies, which may facilitate future discoveries of novel biomarkers for disease.
The Mediterranean diet has been widely promoted and may be associated with chronic disease prevention and a better overall health status. The aim of this study was to evaluate whether the ...Mediterranean diet score inversely predicted total or cause-specific mortality in a prospective population study in Northern Sweden (Västerbotten Intervention Program). The analyses were performed in 77,151 participants (whose diet was measured by means of a validated FFQ) by Cox proportional hazard models adjusted for several potential confounders. The Mediterranean diet score was inversely associated with all-cause mortality in men HR = 0.96 (95% CI = 0.93, 0.99) and women HR = 0.95 (95% CI = 0.91, 0.99), although not in obese men. In men, but not in women, the score was inversely associated with total cancer mortality HR = 0.92 (95% CI = 0.87, 0.98), particularly for pancreas cancer HR = 0.82 (95% CI = 0.68, 0.99). Cardiovascular mortality was inversely associated with diet only in women HR = 0.90 (95% CI = 0.82, 0.99). Except for alcohol HR = 0.83 (95% CI = 0.76, 0.90) and fruit intake HR = 0.90 (95% CI = 0.83, 0.98), no food item of the Mediterranean diet score independently predicted mortality. Higher scores were associated with increasing age, education, and physical activity. Moreover, healthful dietary and lifestyle-related factors additively decreased the mortality likelihood. Even in a subarctic region, increasing Mediterranean diet scores were associated with a longer life, although the protective effect of diet was of small magnitude compared with other healthful dietary and lifestyle-related factors examined.
A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci ...involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the ...need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case–control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (
RTEL
), 5p15.33 (
TERT
), and 9p21.3 (
CDKN2BAS
), and consistent association signals for the remaining four at 7p11.2 (
EGFR
both loci), 8q24.21 (
CCDC26
) and 11q23.3 (
PHLDB1
). The direction and magnitude of the signal were consistent for samples from cohort and case–control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33;
RTEL
) and rs2736100 (5p15.33,
TERT
) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
Background:
The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction ...between these two factors has been proposed.
Objectives:
The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.
Methods:
Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed.
Results:
The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found.
Conclusions:
We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.
To evaluate plant sterol intake estimated with the eighty-four-item Northern Sweden FFQ against repeated 24 h dietary recalls (24-HDR) as the reference method.
Randomly recruited participants from ...the Västerbotten Intervention Programme (VIP) responded to an FFQ (FFQ1). Over the subsequent 12 months, ten repeated 24-HDR were carried out. After this, a second FFQ (FFQ2) was completed.
Västerbotten county, northern Sweden.
Ninety-six men and ninety-nine women.
The Pearson correlation coefficient for absolute total plant sterol intake estimated with FFQ1 and 24-HDR was 0.58 and 0.55 for the men and women, respectively. Cross-classification of participants into quartiles of absolute plant sterol intake estimated with FFQ1 and 24-HDR showed that 90% of the men and 83% of the women were classified into the same or an adjacent quartile. For energy-adjusted plant sterol intake, 71% of the men and 74% of the women were classified into the same or an adjacent quartile. The agreement for cross-classification of participants into quartiles between FFQ1 and FFQ2 was good for both absolute and energy-adjusted plant sterol intake.
The FFQ is able to capture absolute plant sterol intake to the same extent as other nutrients, and to rank individuals according to both their absolute and energy-adjusted plant sterol intake. The reproducibility of the FFQ was good, suggesting that the method is reliable. This makes it possible to use plant sterol data from the FFQ in large-scale studies of the association between plant sterol intake and disease.
A biobank may be defined as the long-term storage of biological samples for research or clinical purposes. In addition to storage facilities, a biobank may comprise a complete organization with ...biological samples, data, personnel, policies, and procedures for handling specimens and performing other services, such as the management of the database and the planning of scientific studies. This combination of facilities, policies, and processes may also be called a biological resource center (BRC) ( www.iarc.fr ). Research using specimens from biobanks is regulated by European Union (EU) recommendations (Recommendations on Research on Human Biological Materials. The draft recommendation on research on human biological materials was approved by CDBI at its plenary meeting on 20 October 2005) and by voluntary best practices from the U.S. National Cancer Institute (NCI) ( http://biospecimens.cancer.gov ) and other organizations. Best practices for the management of research biobanks vary according to the institution and differing international regulations and standards. However, there are many areas of agreement that have resulted in best practices that should be followed in order to establish a biobank for the custodianship of high-quality specimens and data.
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