Biomarkers of dementia in the general population

Prof. Dr. Hans Jörgen Grabe

Areas of investigation/research focus

1. Genetic factors in Dementia

At the University Medicine of Greifswald we have extensive clinical phenotype data and whole body MRI-images from the population-based cohorts SHIP and TREND (SHIP/TREND, n> 8000) and inpatients cohorts (GANI_MED, n>4500). Additionally, we use MRI data from the UKBiobank, German National Cohort and other cohorts as well.

We have coordinated the German activities in the JPND project “Brain Imaging, cognition, Dementia and next generation GEnomics: a Transdisciplinary approach to search for risk and protective factors of neurodegenerative disease” (BRIDGET). Together with international partners, we search for common and rare genetic variants of AD and will establish new brain imaging markers for early risk assessment of dementia. Additionally, we perform genome-wide sequencing for the determination of the degree of methylation (Methyl-C sequencing). In the NIH-funded follow-up project „cross-cohort-collaboration“ (CCC) we seek novel insight into the interaction of somatic risk factors like pulmonary or liver diseases in the pathogenesis of dementia.

Along with the molecular parameters clinical and brain imaging phenotypes will be analyzed. My group is responsible for new structural MRI markers (see 2.)

2. Novel MRI markers of ageing

Based on previous neuroimaging studies we apply a high-dimensional pattern classification algorithm to MRI-based FreeSurfer data to generate the FS-BA score for brain aging in SHIP subjects and the FS-AD score for the identification of Alzheimer´s like brain atrophy pattern. Further on, we use DTI and other markers like white matter hyperintensities (WMH). These scores are now used in biomarker research for early AD

3. Urine Metabolomics in Dementia

Based on NMR-measured urine metabolites we have established a metabolic age score indicating biological ageing as departure from chronological age. As part of this research we have identified metabolites that are associated with ageing and gray matter loss in the brain. These metabolites will be tested in special ageing cohorts (e.g. DELCODE) for their association to Alzheimer´s disease. The working group of Prof. Johannes Hertel is performing in-depth analyses (shot-gun sequencing) of the human gut microbiome and its metabolic activities to understand the contribution of these microbial factors for brain health and neurodegeneration.

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