Refine
Document Type
- Article (8)
Language
- English (8)
Has Fulltext
- yes (8)
Is part of the Bibliography
- no (8)
Keywords
- - (4)
- Alzheimer’s disease (2)
- APOE ε4 (1)
- BDNF (1)
- MDD (1)
- NMR metabolomics (1)
- TREML2 (1)
- alpha diversity (1)
- amyloid beta (1)
- anthropometry (1)
Institute
- Institut für Community Medicine (3)
- Klinik für Psychiatrie und Psychotherapie (3)
- Institut für Klinische Chemie und Laboratoriumsmedizin (2)
- Kliniken und Polikliniken für Innere Medizin (2)
- Institut für Diagnostische Radiologie und Neuroradiologie (1)
- Institut für Medizinische Psychologie (1)
- Klinik und Poliklinik für Augenheilkunde (1)
- Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie/Plastische Operationen (1)
- Klinik und Poliklinik für Orthopädie und Orthopädische Chirurgie (1)
- Poliklinik für Kieferorthopädie, Präventive Zahnmedizin und Kinderzahnheilkunde (1)
Publisher
- MDPI (8) (remove)
Although the common pathology of Alzheimer’s disease (AD) and white matter hyperintensities (WMH) is disputed, the gene TREML2 has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (APOE) ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant’s AD-related brain atrophy. In our study, increased whole-blood TREML2 gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The APOE status did not influence the associations. In sum, TREML2 robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin TREML2’s role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight TREML2 as a worthwhile target for disentangling the two pathologies.
APOE ε4 in Depression-Associated Memory Impairment—Evidence from Genetic and MicroRNA Analyses
(2022)
(1) Background: The aim of this study was to replicate a reported interaction between APOE ε4 status and depression on memory function in two independent, nondemented samples from the general population and to examine the potential role of circulating plasma miRNAs. (2) Methods: The impact of the APOE ε4 allele on verbal memory and the interaction with depression is investigated in two large general-population cohorts from the Study of Health in Pomerania (SHIP, total n = 6286). Additionally, biological insights are gained by examining the potential role of circulating plasma miRNAs as potential epigenetic regulators. Analyses are performed using linear regression models adjusted for relevant biological and environmental covariates. (3) Results: Current depression as well as carrying the APOE ε4 allele were associated with impaired memory performance, with increasing effect for subjects with both risk factors. In a subcohort with available miRNA data subjects with current depressive symptoms and carrying APOE e4 revealed reduced levels of hsa-miR-107, a prominent risk marker for early Alzheimer’s Disease. (4) Conclusions: Our results confirm the effect of depressive symptoms and APOE ε4 status on memory performance. Additionally, miRNA analysis identified hsa-miR-107 as a possible biological link between APOE ε4, depressive symptoms, and cognitive impairment.
The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.
Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.
Background: The global obesity epidemic is a major public health concern, and accurate diagnosis is essential for identifying at-risk individuals. Three-dimensional (3D) body scanning technology offers several advantages over the standard practice of tape measurements for diagnosing obesity. This study was conducted to validate body scan data from a German population-based cohort and explore clinical implications of this technology in the context of metabolic syndrome. Methods: We performed a cross-sectional analysis of 354 participants from the Study of Health in Pomerania that completed a 3D body scanning examination. The agreement of anthropometric data obtained from 3D body scanning with manual tape measurements was analyzed using correlation analysis and Bland–Altman plots. Classification agreement regarding abdominal obesity based on IDF guidelines was assessed using Cohen’s kappa. The association of body scan measures with metabolic syndrome components was explored using correlation analysis. Results: Three-dimensional body scanning showed excellent validity with slightly larger values that presumably reflect the true circumferences more accurately. Metabolic syndrome was highly prevalent in the sample (31%) and showed strong associations with central obesity. Using body scan vs. tape measurements of waist circumference for classification resulted in a 16% relative increase in the prevalence of abdominal obesity (61.3% vs. 52.8%). Conclusions: These results suggest that the prevalence of obesity may be underestimated using the standard method of tape measurements, highlighting the need for more accurate approaches.