AG – Otto - Neurochemistry and Neurodegeneration


The neurochemical differential and early diagnosis of neurodegenerative disease represents one focus of our interdisciplinary group. Using a proteomic approach, we attempt to detect potential markers in cerebrospinal fluid. These markers are characterised and further investigated with regard to their differential diagnostic and pathophysiological relevance. As a model, we first concentrated on the differential diagnosis of Creutzfeldt-Jakob disease. We now also use these methods for the diagnosis of Alzheimer’s disease, Lewy-body disease, Parkinson´s disease dementia, frontotemporal dementia and amyotrophic lateral sclerosis (European reference lab for the diagnosis of neurodegenerative diseases).
As one our our key diagnostic markers we put a spezial focus on the biological function of 14-3-3 proteins in the nervous system. Here we generated a 14-3-3 gamma knock-out mouse which is now characterized in different experimental settings. Furtherly we investigate the amyloid-precursor processing and especially its differential diagnostic use in various dementias.
In a nationwide clinical study we investigate the use of different therapeutics for patients with Creutzfeldt-Jakob disease. Most recently we could with other German centers establish a consortium to investigate all forms of frontotemporal lobar degenerations (


Biacore binding studies
clincal proteomics (IPG-2D-PAGE, DIGE, iTraq)
14-3-3 protein biology (deletion mutant mice)
APP-processing (urea gel electrophoresis)
monoclonal antibodies
primary cell culture (mice, chicken)
Neurochemical diagnosis of neurodegenerative disease (14-3-3, Tau-protein, Abeta-Peptides, S-100B, H-FABP, alpha synuclein)
Sample bank of CSF and Serum (Alzheimer´s disease, Parkinson´s disease, Frontotemporal dementias, Prion diseases, Amyotrophic lateral sclerosis)

2D-picture of CSF (DIGE and silver)



BMBF: Establishment of a national network for patients with frontotemporal lobar degeneration (

EU: Nanosystems for the early and differential diagnosis of neurodegenertive diseases – NADINE

Stiftung Baden-Württenberg: Validation of biomarkers in Parkinson´s disease dementia
Thierry Latran Foundation: Proteomic approaches for subtyping of ALS patients
BMBF: Biobanking approaches for motoneuron diseaes
EU/JNPD: Sampling and biomarker OPtimization and Harmonization In ALS and other motor neuron diseases – SOPHIA
EU/JNPD: Biomarkers for Alzheimer’s disease and Parkinson’s disease – Biomark-ADP
BIU: Pathophysiological and diagnostic approaches toward Parkinson´s disease and Parkinson`s disease dementia

BMWi: Development of an assay for Alzheimer´s disease

Landesstiftung Baden-Württenberg (foundation of state Baden-Wuerttenberg): proteomic applications in the early diagnosis of parkinson´s disease
EU: Development of a pre-clinical blood test for prion diseases
EU: Clinical Neuroproteomics of Neurodegenerative
EU: Microfluid total analysis system for the early diagnosis of neurodegenerative disorders
EU: Erasmus mundus program: planning and organization of European master for tropical neurology
BMBF: Follow-up and therapy study on patients with Creutzfeldt-Jakob disease
DFG/CMBP: Proteomanalyse zur Diagnose von Parkinson-Syndromen
BMGS: Labordiagnostische Verfahren zur Früherkennung der transmissiblen spongiformen Enzephalopathien
BMBF: Frühdiagnose transmissibler spongiformer Enzephalopathien durch Proteomanalyse
DFG/CMBP: Proteomanalyse bei Neurodegenerativen Erkrankungen
EU: Diagnosis and Function of 14-3-3 Proteins in CJD
VerUm Stiftung: Untersuchung zur pathophysiologisch fundierten klinisch-chemischen Früh- und Differentialdiagnostik dementieller Erkrankungen
Asta-Medica: Therapiestudie mit Flupirtin bei Patienten mit Creutzfeldt-Jakob Krankheit
Byk-Sangtec: Wertigkeit von S-100 beim Schlaganfall; Wertigkeit der S-100 Bestimmung bei Störung der Blut-Hirn-Schranke

Selected Publications

Otto M, Bowser R, Turner M, Berry J, Brettschneider J, Connor J, Costa J, Cudkowicz M, Glass J, Jahn O, Lehnert S, Malaspina A, Parnetti L, Petzold A, Shaw P, Sherman A, Steinacker P, Süssmuth S, Teunissen C, Tumani H, Wuolikainen A, Ludolph A. Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS. Amyotroph Lateral Scler 2012; 13: 1-10.

Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung HP, Hemmer B, Hohlfeld R, Otto M, Stangel M, Wildemann B, Zettl UK. Revised McDonald criteria: The persisting importance of cerebrospinal fluid analysis. Ann Neurol 2011; 70: 520

Steinacker P, Hawlik A, Lehnert S, Jahn O, Meier S, Gorz E, Braunstein KE, Krzovska M, Schwalenstocker B, Jesse S, Propper C, Bockers T, Ludolph A, Otto M. Neuroprotective function of cellular prion protein in a mouse model of amyotrophic lateral sclerosis. Am J Pathol 2010a; 176: 1409-20.

Steinacker P, Hendrich C, Sperfeld AD, Jesse S, von Arnim CA, Lehnert S, Pabst A, Uttner I, Tumani H, Lee VM, Trojanowski JQ, Kretzschmar HA, Ludolph A, Neumann M, Otto M. TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch Neurol 2008; 65: 1481-7.

Brechlin P, Jahn O, Steinacker P, Cepek L, Kratzin H, Lehnert S, Jesse S, Mollenhauer B, Kretzschmar HA, Wiltfang J, Otto M. Cerebrospinal fluid-optimized two-dimensional difference gel electrophoresis (2-D DIGE) facilitates the differential diagnosis of Creutzfeldt-Jakob disease. Proteomics 2008; 8: 4357-4366.
Sättler MB, Williams SK, Neusch C, Otto M, Pehlke JR, Bahr M, Diem R. Flupirtine as neuroprotective add-on therapy in autoimmune optic neuritis. Am J Pathol 2008; 173: 1496-507.

Otto M, Lewczuk P, Wiltfang J. Neurochemical approaches of cerebrospinal fluid diagnostics in neurodegenerative diseases. Methods 2008; 44: 289-98.
Guerchet M, Houinato D, Paraiso MN, von Ahsen N, Nubukpo P, Otto M, Clement JP, Preux PM, Dartigues JF. Cognitive Impairment and Dementia in Elderly People Living in Rural Benin, West Africa. Dement Geriatr Cogn Disord 2009; 27: 34-41

Steinacker P, Reim, K, Schwarz, A, Brechlin, P, Jahn, O, Kratzin, H, Aitken, A, Wiltfang, J, Aguzzi, A, Bahn, E, Baxter, HC, Brose, N, Otto, M (2005) Unchanged survival curves of 14-3-3 gamma knock-out mice after inoculation with pathological prion protein. Mol Cell Biol. 25: 1339-1346.

Meier A, Mollenhauer B, Cohrs S, Rodenbeck A, Jordan W, Meller J, Otto M. Normal hypocretin-1 (orexin-A) levels in the cerebrospinal fluid of patients with Huntington's disease. Brain Res 2005; 1063: 201-3.

Otto M, Cepek, L, Ratzka, P, Doehlinger, S, Boekhoff, I, Wiltfang, J, Irle, E, Pergande, G, Ellers-Lenz, B, Windl, O, Kretzschmar, HA, Poser, S, Prange, H (2004) Efficacy of Flupirtine on Cognitive Function in Patients with CJD: a double blind study. Neurology 62: 714-718.

Steinacker P, Mollenhauer, M, Bibl, M, Cepek, L, Esselmann, H, Brechlin, P, Lewczuk, P, Poser, S, Kretzschmar, HA, Wiltfang, J, Trenkwalder, C, Otto, M (2004) Heart fatty acid binding protein as a potential diagnostic marker for neurodegenerative diseases. Neurosci Lett 3: 36-39.

Wiltfang J, Esselmann, H, Smirnov, A, Bibl, M, Cepek, L, Steinacker, P, Mollenhauer, B, Buerger, K, Hampel, H, Paul, S, Neumann, M, Maler, M, Zerr, I, Kornhuber, J, Kretzschmar, HA, Poser, S, Otto, M (2003) beta-amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Ann Neurol 54: 263-267.

Otto M, Wiltfang, J, Cepek, L, Neumann, M, Mollenhauer, B, Steinacker, P, Ciesielczyk, B, Schulz-Schaeffer, W, Kretzschmar, HA, Poser, S (2002) Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58: 192-197.

Otto M, Holthusen, S, Bahn, E, Söhnchen, N, Wiltfang, J, Geese, R, Fischer, A, Reimers, CD (2000) Boxing and running lead to a rise in serum levels of S-100B protein. Int J Sports Med 21: 551-555.

Otto M, Wiltfang, J, Schütz, E, Zerr, I, Otto, A, Pfahlberg, A, Gefeller, O, Uhr, M, Giese, A, Weber, T, Kretzschmar, HA, Poser, S (1998) Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study. BMJ 316: 577-582.

All Publications

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