The Section for Dementia Research of the Department of Cellular Neurology and the University Clinic for Psychiatry and Psychotherapy is headed by Prof. Dr. Christoph Laske. The section consists of a Research Unit and collaborates with an outpatient Memory Clinic.
1. Longitudinal analysis of clinical, neuropsychological, and imaging modalities in familial Alzheimer ́s disease and to use these results for the further understanding of sporadic Alzheimer ́s disease.
2. Identification and validation of new biofluid biomarkers for Alzheimer ́s disease.
3. Identification of new imaging biomarkers for Alzheimer`s diesease.
To this end we are recruiting participants from our Memory Clinic. From these individuals we are typically collecting blood and CSF samples consistent with the guidelines of the Neuro-Biobank of the University Clinic and the DZNE Tübingen. In addition, urine and tear fluid are collected of some of these individuals. Commercially available immunoassays are used or newly developed in collaboration with the Fluid Disease Biomarkers group. The neuroimaging is done in collaboration with the Max Planck Institute for Biological Cybernetics and the Department of Biomedical Magnetic Resonance in Tübingen (Prof. K. Scheffler).
DIAN stands for “Dominantly Inherited Alzheimer Network”, the international network for dominantly inherited Alzheimer ́s disease. The study was founded in the USA in 2008 in order to investigate genetic forms of Alzheimer ́s disease. Individuals from families with inherited forms of Alzheimer ́s disease (the autosomal dominant form or the related Aß amyloid angiopathy) are to participate in this study. These rare forms of Alzheimer ́s disease are caused by mutations in one of three genes (APP, PSEN1 or PSEN2). In the first phase of the DIAN study, affected individuals are identified and examined via multimodal diagnostics (e.g. PET-PIB; MRI; biofluids; neuropsychology) in regard to preclinical changes. In the second and future phase, treatment trials are planned. The goal is to treat the disease preventively already at a preclinical stage, i.e. before any symptoms appear. In Germany and Tübingen we joined the DIAN study in 2012. Since then we recruited over 20 subjects and have participated in the scientific assessement of the worldwide collected data (e.g. Laske et al., submitted).
Using multiple immunoassays, we have found that by means of three biomarkers measured in the blood (Cortisol, von Willebrand factor, oxidized LDL-antibodies) Alzheimer patients can be distinguished from healthy controls with a test accuracy of more than 80% (Laske et al., Int J Neuropsychopharmacol 2011). This minimally-invasive and low-cost method may be suitable for the screening of Alzheimer patients. More recently, we measured the activity of calpain - a calcium-dependent protease known to be associated with Alzheimer pathology and with neuronal apoptosis - in Alzheimer patients and in healthy elderly controls. Interestingly, calpain activity was significantly decreased in serum and plasma and significantly increased in CSF of Alzheimer patients compared to healthy controls (Laske et al., Alzheimer`s & Dementia 2014). Thus, calpain activity could be a novel biomarker and treatment target for Alzheimer`s disease.
To identify new imaging biomarkers for Alzheimer`s diesease, we are using high resolution structural magnetic resonance imaging (9.4T MRI). Ultra-high field 9.4T MRI offers superior signal-to-noise and spatial resolution relative to any other noninvasive imaging technique. In an ongoing project we are performing 9.4T MRI in Alzheimer patients with different disease stages and in healthy controls.
Contact: Christoph Laske
Laske C, Sohrabi HR, Jasielec MS, Müller S, Koehler NK, Gräber S, Förster S, Drzezga A, Mueller-Sarnowski F, Danek A, Jucker M, Bateman RJ, Buckles V, Saykin AJ, Martins RN, Morris JC, Dominantly Inherited Alzheimer Network Dian (2015) Diagnostic Value of Subjective Memory Complaints Assessed with a Single Item in Dominantly Inherited Alzheimer's Disease: Results of the DIAN Study. Biomed Res Int 2015:828120 (Abstract)
Laske C, Stellos K, Kempter I, Stransky E, Maetzler W, Fleming I, Randriamboavonjy V (2015) Increased cerebrospinal fluid calpain activity and microparticle levels in Alzheimer's disease. Alzheimers Dement 11:465-74 (Abstract)
Laske C, Sohrabi HR, Frost SM, López-de-Ipiña K, Garrard P, Buscema M, Dauwels J, Soekadar SR, Mueller S, Linnemann C, Bridenbaugh SA, Kanagasingam Y, Martins RN, O'Bryant SE (2015) Innovative diagnostic tools for early detection of Alzheimer's disease. Alzheimers Dement 11:561-78 (Abstract)
O’Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Bazenet C, Soares H, Lovestone S, Hampel H, Montine T, Blennow K, Foroud T, Carrillo M, Graff-Radford N, Laske C, Breteler M, Shaw L, Trojanowski JQ, Schupf N, Rissman RA, Fagan A, Barnham K, Oberoi P, Umek R, Weiner MW, Grammas P, Posner H, Martins R for the STAR-B and BBBIG working groups (2015) Guidelines for the Standardization of Preanalytic Variables for Blood-Based Biomarker Studies in Alzheimer’s Disease Research. Alzheimers Dement 11:549-60 (Abstract)
Stamatelopoulos K, Sibbing D, Rallidis LS, Georgiopoulos G, Stakos D, Braun S, Gatsiou A, Sopova K, Kotakos C, Varounis C, Tellis CC, Kastritis E, Alevizaki M, Tselepis AD, Alexopoulos P, Laske C, Keller T, Kastrati A, Dimmeler S, Zeiher AM, Stellos K (2015) Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease. J Am Coll Cardiol 65:904-16 (Abstract)
Universitätsklinikum für Psychiatrie und Psychotherapie
Hertie-Institut für klinische Hirnforschung
Abteilung Zellbiologie neurologischer Erkrankungen
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