Completed Projects · Neuroscience

Team TNA

Tau-Mediated Neurodegeneration in Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia worldwide, affecting millions of patients, with no therapeutic options available to date. While amyloid plaques have long been recognized as hallmarks of the disease, recent evidence suggests that abnormal post-translational modifications of the Tau protein are strongly involved in disease manifestation and progression. In Alzheimer’s disease, Tau is unable to perform its normal function in the stabilization of microtubules and is prone to hyperphosphorylation, aggregation and secretion.

We study the network of Tau post-translational modifications, interactions between different types of modifications, and their impact on Tau function and dysfunction in the disease state using materials obtained from sporadic Alzheimer’s disease patients as well as neurons derived from induced pluripotent stem cells. Analytical and biochemical approaches and screening methods are used to identify tractable therapeutic targets in Tau post-translational modification pathways that can serve as starting points for the development of therapeutic agents. We aim to define a characteristic signature of pathologic Tau post-translational modifications that will serve as a biomarker to support the diagnosis and monitor the progression of Alzheimer’s disease.


  1. Ercan E, Eid S, Weber C, Kowalski A, Bichmann M, Behrendt A, Matthes F, Krauss S, Reinhardt P, Fulle S, Ehrnhoefer DE (2017):
    A validated antibody panel for the characterization of tau post-translational modifications
    Molecular Neurodegeneration 12(1)
  2. Schöndorf DC, Elschami M, Schieck M, Ercan-Herbst E, Weber C, Riesinger Y, Kalman S, Steinemann D, Ehrnhoefer DE (2018):
    Generation of an induced pluripotent stem cell cohort suitable to investigate sporadic Alzheimer’s Disease
    Stem Cell Research 34
  3. Behrendt A, Bichmann M, Ercan-Herbst E, Haberkant P, Schöndorf DC, Wolf M, Fahim SA, Murolo E, Ehrnhoefer DE (2019):
    Asparagine endopeptidase cleaves tau at N167 after uptake into microglia
    Neurobiology of Disease 130
  4. Ercan-Herbst E, Ehrig J, Schöndorf DC, Behrendt A, Klaus B, Gomez Ramos B, Prat Oriol N, Weber C, Ehrnhoefer DE (2019):
    A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer’s disease brain
    Acta Neuropathologica Communications 7(1)
  5. Garc√≠a-Cham√© MA, Guti√©rrez-Sanz √ď, Ercan-Herbst E, Haustein N, Filipiak MS, Ehrnh√∂fer DE, Tarasov A (2020):
    A transistor-based label-free immunosensor for rapid detection of tau protein
    Biosensors and Bioelectronics
  6. Erica Barini, Gudrun Plotzky, Yulia Mordashova, Jonas Hoppe, Esther Rodriguez-Correa, Sonja Julier, Florie LePrieult, Ina Mairhofer, Mario Mezler, Sandra Biesinger, Miroslav Cik, Marcus W Meinhardt, Ebru Ercan-Herbst, Dagmar Ehrnhoefer, Andreas Striebinger, Karen Bodie, Corinna Klein, Laura Gasparini, Kerstin Schlegel (2022):
    Tau in the brain interstitial fluid is fragmented and seeding-competent
    Neurobiology of Aging
  7. Maria Bichmann, Nuria Prat Oriol, Ebru Ercan-Herbst, David C. Sch√∂ndorf, Borja Gomez Ramos, Vera Schw√§rzler, Marie Neu, Annabelle Schl√ľter, Xue Wang, Liang Jin, Chenqi Hu, Yu Tian, Janina S. Ried, Per Haberkant, Laura Gasparini, Dagmar E. Ehrnhoefer (2021):
    SETD7-mediated monomethylation is enriched on soluble Tau in Alzheimer’s disease
    Molecular Neurodegeneration
  8. Reinhardt L, Musacchio F, Bichmann M, Behrendt A, Ercan-Herbst E, Stein J, Becher I, Haberkant P, Mader J, Schöndorf DC, Schmitt M, Korffmann J, Reinhardt P, Pohl C, Savitski M, Klein C, Gasparini L, Fuhrmann M, Ehrnhoefer DE (2023): Dual truncation of tau by caspase-2 accelerates its CHIP-mediated degradation
    Neurobiology of Disease, 182
The research of this team was kindly sponsored by AbbVie.