Prof. Dr. Manuela Neumann

Prof. Dr. Manuela Neumann

Group Leader
Manuela Neumann is chair of the Department of Neuropathology at the Medical Faculty of the Eberhard Karls University of Tuebingen and medical director of the Department of Neuropathology, University Hospital Tübingen

German Center for Neurodegenerative Diseases (DZNE)
Otfried-Müller-Str. 23
72076 Tübingen

+49 (0) 7071 / 9254-100
+49 (0) 7071 / 9254-900

Group members

Name Phone
Dr. Jasvir Kaur, Postdoc +49 (0) 7071 / 9254-125
Dr. Petra Frick, Scientific Associate +49 (0) 7071 / 9254-121
Further group memebers (Uni/third party funding)
Dr. Chiara Valori, Postdoc +49 (0) 7071 / 9254-122
Chie-Yu Cheng, PhD student
Janna Lischewski, Biological technical Assistant

Curriculum Vitae

Manuela Neumann studied medicine at the University of Munich (LMU) and University of Goettingen. For her doctoral thesis, she performed studies on the prion protein gene and its role in familial and transmissible prion diseases (supervisor Prof. Dr. Kretzschmar). She received her training as a specialist in neuropathology at the Institute of Neuropathology, University Göttingen and Munich. During this time she was also the scientific coordinator for the German brain bank network "Brain-Net". From 2005-2006 she was a visiting scientist at the laboratory of Drs John Trojanowski and Virginia Lee at the Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA. After her return to the Institute of Neuropathology she worked as independent group leader and habilitated in the same year at the LMU on the molecular neuropathology of α-synucleinopathies and tauopathies. In 2008 she was appointed Assistant Professor of Experimental Neuropathology at the University of Zurich. In June 2012 she accepted an appointment as chair of neuropathology at the University of Tübingen and the Center for Neurodegenerative Disease Research.

Prof. Neumann’s main research area is the molecular pathology of neurodegenerative diseases with focus on frontotemporal dementia and amyotrophic lateral sclerosis. She was honored for her work with several awards, including the prestigious research award from the Hans & Ilse Breuer Foundation in 2012.

Professor Neumann is a member of the editorial board of Acta Neuropathologica.

Selected publications

Advances in understanding the molecular basis of frontotemporal dementia.

Rademakers R, Neumann M, and Mackenzie IR (2012). Nat Rev Neurol 8:423-434.

Neuropathological background of phenotypical variability in frontotemporal dementia.

Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM, and Dickson DW (2011). Acta Neuropathol 122:137-153.

FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations.

Neumann M, Bentmann E, Dormann D, Jawaid A, DeJesus-Hernandez M, Ansorge O, Roeber S, Kretzschmar HA, Munoz DG, Kusaka H, Yokota O, Ang L-C, Bilbao J, Rademakers R, Haass C, and Mackenzie IRA (2011). Brain 134:2595-2609.

Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone.

Custer SK, Neumann M, Lu H, Wright AC, and Taylor JP (2010). Hum Mol Genet 19:1741-1755.

ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.

Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, and Haass C (2010). EMBO J 29:2841-2857.

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia.

Mackenzie IR, Rademakers R, and Neumann M (2010). Lancet Neurol 9:995-1007.

Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update.

Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, and MannDM (2010). Acta Neuropathol 119:1-4.

Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations.

Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, and Mann DM (2009). Acta Neuropathol 117:15-18.

A new subtype of frontotemporal lobar degeneration with FUS pathology.

Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, and Mackenzie IR (2009). Brain 132:2922-2931.

Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease.

Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, and Mackenzie IR (2009). Acta Neuropathol 118:605-616.

FUS pathology in basophilic inclusion body disease.

Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, Kuroda S, and Mackenzie IR (2009). Acta Neuropathol 118:617-627.

Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies.

Neumann M, Kwong LK, Lee EB, Kremmer E, Flatley A, Xu Y, Forman MS, Troost D, Kretzschmar HA, Trojanowski JQ, and Lee VM (2009). Acta Neuropathol 117:137-149

The molecular basis of frontotemporal dementia.

Neumann M, Tolnay M, and Mackenzie IR (2009). Expert Rev Mol Med 11:e23.

TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions.

Cairns NJ, Neumann M, Bigio EH, Holm IE, Troost D, Hatanpaa KJ, Foong C, White CL, 3rd, Schneider JA, Kretzschmar HA, Carter D, Taylor-Reinwald L, Paulsmeyer K, Strider J, Gitcho M, Goate AM, Morris JC, Mishra M, Kwong LK, Stieber A, Xu Y, Forman MS, Trojanowski JQ, Lee VM, and Mackenzie IR (2007). Am J Pathol 171:227-240.

Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration

Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL, 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, and Mann DM (2007). Acta Neuropathol (Berl) 114:5-22.

TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations.

Neumann M, Mackenzie IR, Cairns NJ, Boyer PJ, Markesbery WR, Smith CD, Taylor JP, Kretzschmar HA, Kimonis VE, and Forman MS (2007).  J Neuropathol Exp Neurol 66:152-157.

Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, and Lee VM (2006). Science 314:130-133.

The complete list of publications is found here.

Areas of investigation/research focus

Fig. 1: Abnormal accumulation of TDP-43 (Pfeil) in spinal cord motor neuron in a patient with amyotrophic lateral sclerosis. Source: M. Neumann
Fig. 1: Abnormal accumulation of TDP-43 (Pfeil) in spinal cord motor neuron in a patient with amyotrophic lateral sclerosis. Source: M. NeumannClick on the magnifying glass for a large image.

1. Frontotemporal dementia and amyotrophic lateral sclerosis

The research interest of my lab is on elucidating the molecular pathomechanisms underlying neurodegenerative diseases, focusing on the two neurodegenerative diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).

FTD is the third most common cause of dementia in general, and the second most common in the presenile group (onset <65 years). Amyotrophic lateral sclerosis (ALS) is the most common neuromuscular disease. For both diseases, there is currently no effective therapy.

With the discoveries of new key proteins and new disease genes in the last couple of years, our understanding of the underlying pathogenic mechanisms in ALS and FTD has changed dramatically.

One seminal discovery was the identification of TDP-43, a DNA / RNA-binding protein, as aggregating protein in most forms of FTD and ALS (Figure 1). Based on that, FUS, and more recently TAF15 and EMS, were identified and characterized as additional DNA / RNA-binding proteins playing a crucial role in other subtypes of FTD and ALS.

Our research goal is now to decipher the mechanisms leading to TDP-43 and FUS-associated cell death in FTD and ALS and, based on that, the development of new therapeutic approaches and new biomarkers for clinical diagnostics.

To achieve this, we use a broad methodological spectrum ranging from histological and proteomic analysis of postmortem tissue from patients with these disorders, to cell culture and molecular biology approaches to the generation and analysis of transgenic mouse models.

Specific objectives / projects are:

  1. Identification of pathomechanistically relevant posttranslational modifications of TDP-43 and FUS from postmortem tissue of patients and model systems using proteomics and mass spectrometry methods
  2. Identification of relevant enzymes / pathways involved in posttranslational modifications as potential drug-targets
  3. Complete characterization of the proteome of the pathological inclusions in human TDP-43 and FUS diseases
  4. Generation of transgenic mouse models mimicking essential pathological aspects of human TDP-43 and FUS diseases.
  5. Identification of mRNA and miRNA targets of TDP-43 and FUS and validation of their pathogenetic relevance

2. Development of a brain tissue bank for neurodegenerative diseases

Despite advances in research and diagnosis of neurodegenerative diseases and development of model systems, the direct investigation of human brain tissue from patients with neurodegenerative disease cannnot be replaced by any other investigation method. Histological and biochemical examination of the human brain is key to decipher disease processes and validate pathways identified in model systems and to develop more accurate diagnostic procedures.

Therefore, our goal is to establish a high-quality brain tissue bank, with standardized protocols for analysis and sampling of postmortem tissue of patients with neurodegenerative diseases, and provision of tissue for scientific questions to research groups within the DZNE.

The cooperation partner's homepage can be found here.