Universitat Dusseldorf Heinrich-Heine, Germany
Dieter Willbold studied biochemistry in Tubingen (Germany), Bayreuth (Germany) and Boulder (Colorado, USA). He completed his PhD in 1994 at the University of Bayreuth. After some more years in Bayreuth and a couple of research visits, e.g. at the Sackler School of Medicine of the Tel-Aviv University, he headed a junior research group at the Institute for Molecular Biotechnology in Jena. In 2001 Willbold became an associate Professor at the Heinrich-Heine-University of Dusseldorf. Since 2004, he is full professor at the Institute of Physical Biology in Dusseldorf and Director of the Institute of Complex Systems in the Research Centre Julich.
Alzheimer’s disease (AD) is a fatal neurodegenerative and progressive disorder. Currently, no reliable biomarkers for pre-symptomatic diagnosis or therapy monitoring are available. Recent studies indicate that especially soluble amyloid beta peptide (Aβ) oligomers are the major toxic species during development and progression of AD. Therefore, we suggest that the number of Aβ oligomers in body fluids can be used as the most relevant and direct biomarker for AD. We developed a surface-based fluorescence intensity distribution analysis (sFIDA) assay for specific quantification of Aβ oligomers with single particle sensitivity. We challenged the assay with cerebrospinal fluid (CSF) samples from 14 AD patients and 12 age-matched control subjects. The Aβ oligomer count revealed a surprisingly clear distinction between both groups. All samples of the control group showed homogenously low numbers of Aβ oligomers, while the samples of the AD group exhibited significantly higher levels of Aβ oligomers. The Aβ oligomer levels clearly correlated with the patients’ mini-mental state examination (MMSE) scores. Our results support the idea that Aβ oligomers play a crucial role in AD pathology and in turn can be used as a diagnostic biomarker. The sFIDA assay is able to reliably and specifically quantify Aβ oligomers in human CSF. In addition, the correlation between MMSE scores and Aβ oligomer concentrations in CSF suggests that the quantity of Aβ oligomers in CSF correlates with the severity of the disease. This will allow to evaluate and to monitor anti-Aβ-targeted therapies based on the Aβ oligomer counts in treated individuals.