Disease markers in tissue and blood

At the Werner Siemens Imaging Center in Tübingen, Christoph Trautwein is using state-of-the-art spectroscopy methods to search for tiny molecules in tissue, blood, urine or cerebrospinal fluid. Called “metabolomics”, the new approach has the potential to deepen our knowledge of diseases like dementia, while also promoting early detection.

Be it sugar, fats or hormones: to function properly, our bodies rely on innumerable tiny molecules called metabolites, which are intermediate or end products of metabolic processes. Their exact composition differs from person to person and is determined by genetic factors, but also by age, diet and immune system health.

“Measuring individual metabolites like glucose, lactate or creatinine has long been part of established medical practice,” says Christoph Trautwein, group leader at the Werner Siemens Imaging Center (WSIC) in Tübingen. In the past decade, however, a new research field has begun to take shape, one that goes far beyond measuring a single molecule: metabolomics. The aim is to identify the complete set of metabolites—the metabolom—found in a cell or organism.

Various methods exist for measuring and quantifying metabolites, including nuclear magnetic resonance (NMR) spectroscopy, which Trautwein and his Tübingen research group are using in their work. In NMR, a powerful and uniform magnetic field is applied to excite atomic nuclei, causing their state to change. This then makes it possible for researchers to differentiate various kinds of molecules. “Normally we study samples extracted from tissue, blood serum or urine,” Trautwein says.

Dementia indicators

Concentrations of the different metabolites can serve as indicators of a disease. To illustrate: in a recently published study (1), Trautwein and his team extracted twenty-seven different metabolites from blood serum and forty-five from cerebrospinal fluid and subsequently examined the differences between healthy people and patients suffering from mild cognitive impairment or severe dementia. “We found significant and specific metabolites in each of these three groups,” Trautwein says. This means these kinds of metabolomic measurements could one day help detect dementia, especially as the method correlates well with already known Alzheimer’s disease indicators such as the amyloid beta peptide.

The researchers also believe that so-called lipoproteins—which transport fats and cholesterol in the body—could play an important role in detecting dementia. “We know that, as we age, lipoprotein metabolism can break down and cause atherosclerosis, high blood pressure and cardiovascular diseases,” Trautwein explains, adding, “It’s a factor in dementia and Parkinson’s.” Last year, he and his colleagues published a study (2) that identified clear differences in lipoprotein groups and subgroups between Alzheimer’s patients and healthy individuals.