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Systems Neurodegeneration


Our research focuses on the investigation of the genetic basis, systems neuroscience and paradigmatic therapy approaches in

  • movement disorders (e.g. degenerative ataxias, in particular early-onset ataxias, neurometabolic diseases, and rare complex movement disorders)
  • frontotemporal dementias and other complex dementias (e.g. FTD spectrum diseases, early-onset dementias, rare variants and complex presentations of Alzheimer’s Disease, genetic dementias)
  • motor neuron diseases (Amyotrophic Lateral Sclerosis, in particular genetic variants; ALS-FTD spectrum diseases, lysosomal motor neuron diseases)

We use a broad spectrum of very different methods, reaching from recent next generation sequencing techniques and protein biomarker profiling to deep clinical phenotyping, neuropsychology and pioneering neurorehabilitative and neurogeriatric approaches.

… more information

Research Projects
Outpatient clinics

Early-onset Ataxia Registry


Early onset ataxia (EOA) is a highly heterogeneous group of degenerative and metabolic diseases, mostly due to genetic causes with autosomal-recessive inheritance. This prospective multi-center international registry and bio-database sets off

->  to assess phenotypic characteristics and the natural history of early-onset ataxias and to aggregate large cohorts of early-onset ataxias, thus establishing the prerequisites for upcoming interventional studies.

-> to provide comprehensive genetic and biomarkers characterization of early-onset ataxias

->  LINK

 Merit Bade
Merit Bade MD Student
BSc Lisa Helene Graf
BSc Lisa Helene Graf Speech scientist
07071 29-82061 
 Julia Göddel-Sand
Julia Göddel-Sand MD Student
07071 29-89131 
 Manuela Hauser
Manuela Hauser Biological Technical Assistant
07071 29-81969 
 Kristina Kaufhold
Kristina Kaufhold MD Student
 Eva-Maria Kraus
Eva-Maria Kraus MD Student
07071 29-82060 
 Doreen Müller
Doreen Müller Study Assistant
Research Division Clinical Neurogenetics
07071 29-85376 
M.Sc Selina Reich
M.Sc Selina Reich Project Coordinator
07071 29-85548 
Prof. Dr. Matthis Synofzik
Prof. Dr. Matthis Synofzik Research Group Leader
07071 29-82060 
Dr. med. Dr. rer. nat. Andreas Traschütz
Dr. med. Dr. rer. nat. Andreas Traschütz Medical Doctor
07071 29-82060 
 Dominik Wabersich
Dominik Wabersich MD Student
07071 29-87601 
Dr. Carlo Wilke
Dr. Carlo Wilke Medical Doctor
Research Division Clinical Neurogenetics
07071 29-82060 
 Nicole Zweig
Nicole Zweig Study Assistant
Research Division Clinical Neurogenetics
07071 29-85374 




Farazi Fard MA, Rebelo AP, Buglo E, Nemati H, Dastsooz H, Gehweiler I, Reich S, Reichbauer J, Quintáns B, Ordóñez-Ugalde A, Cortese A, Courel S, Abreu L, Powell E, Danzi M, Martuscelli NB, Bis-Brewer DM, Tao F, Zarei F, Habibzadeh P, Yavarian M, Modarresi F, Silawi M, Tabatabaei Z, Yousefi M, Farpour HR, Kessler C, Mangold E, Kobeleva X, Mueller AJ, Haack TB, Tarnopolsky M, Gan-Or Z, Rouleau GA, Synofzik M, Sobrido MJ, Jordanova A, Schüle R, Zuchner S, Faghihi MA. Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia. Am J Hum Genet. 2019 Apr 4;104(4):767-773. Epub 2019 Mar 28.


Keskin I, Forsgren E, Lehmann M, Andersen PM, Brännström T, Lange DJ, Synofzik M, Nordström U, Zetterström P, Marklund SL, Gilthorpe JD. The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension. Acta Neuropathol. 2019 Mar 12. [Epub ahead of print]


Albrecht F, Mueller K, Ballarini T, Lampe L, Diehl-Schmid J, Fassbender K, Fliessbach K, Jahn H, Jech R, Kassubek J, Kornhuber J, Landwehrmeyer B, Lauer M, Ludolph AC, Lyros E, Prudlo J, Schneider A, Synofzik M, Wiltfang J, Danek A, Otto M; FTLD-Consortium, Schroeter ML. Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging. Cortex. 2019 Feb 25;117:33-40. [Epub ahead of print]


Vogel AP, Stoll LH, Oettinger A, Rommel N, Kraus EM, Timmann D, Scott D, Atay C, Storey E, Schöls L, Synofzik M. Speech treatment improves dysarthria in multisystemic ataxia: a rater-blinded, controlled pilot-study in ARSACS. J Neurol. 2019 May;266(5):1260-1266. Epub 2019 Mar 6.


Lindig T, Bender B, Kumar VJ, Hauser TK, Grodd W, Brendel B, Just J, Synofzik M, Klose U, Scheffler K, Ernemann U, Schöls L. Pattern of Cerebellar Atrophy in Friedreich's Ataxia-Using the SUIT Template. Cerebellum. 2019 Feb 15. [Epub ahead of print]


Pottier C, Ren Y, Perkerson RB 3rd, Baker M, Jenkins GD, van Blitterswijk M, DeJesus-Hernandez M, van Rooij JGJ, Murray ME, Christopher E, McDonnell SK, Fogarty Z, Batzler A, Tian S, Vicente CT, Matchett B, Karydas AM, Hsiung GR, Seelaar H, Mol MO, Finger EC, Graff C, Öijerstedt L, Neumann M, Heutink P, Synofzik M, Wilke C, Prudlo J, Rizzu P, Simon-Sanchez J, […], Mackenzie IRA, van Swieten JC, Dickson DW, Biernacka JM, Rademakers R. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD. Acta Neuropathol. 2019 Feb 9. [Epub ahead of print]


Premi E, Calhoun VD, Diano M, Gazzina S, Cosseddu M, Alberici A, Archetti S, Paternicò D, Gasparotti R, van Swieten J, Galimberti D, Sanchez-Valle R, Laforce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe J, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Cappa S, Sorbi S, Padovani A, Rohrer JD, Borroni B; Genetic FTD Initiative, GENFI. The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint. Neuroimage. 2019 Apr 1;189:645-654. Epub 2019 Feb 1.


Srulijes K, Klenk J, Schwenk M, Schatton C, Schwickert L, Teubner-Liepert K, Meyer M, K C S, Maetzler W, Becker C, Synofzik M. Fall Risk in Relation to Individual Physical Activity Exposure in Patients with Different Neurodegenerative Diseases: a Pilot Study. Cerebellum. 2019 Jan 8. [Epub ahead of print]


Rinaldi L, Delle Donne R, Catalanotti B, Torres-Quesada O, Enzler F, Moraca F, Nisticò R, Chiuso F, Piccinin S, Bachmann V, Lindner HH, Garbi C, Scorziello A, Russo NA, Synofzik M, Stelzl U, Annunziato L, Stefan E, Feliciello A. Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system. Nat Commun. 2019 Jun 12;10(1):2572. doi: 10.1038/s41467-019-10037-y.


Gazzina S, Grassi M, Premi E, Cosseddu M, Alberici A, Archetti S, Gasparotti R, Van Swieten J, Galimberti D, Sanchez-Valle R, Laforce RJ, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler CR, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Sorbi S, Padovani A, Rohrer JD, Borroni B; Genetic FTD Initiative, GENFI. Education modulates brain maintenance in presymptomatic frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2019 Jun 10.


Coarelli G, Schule R, van de Warrenburg BPC, De Jonghe P, Ewenczyk C, Martinuzzi A, Synofzik M, Hamer EG, Baets J, Anheim M, Schöls L, Deconinck T, Masrori P, Fontaine B, Klockgether T, D'Angelo MG, Monin ML, De Bleecker J, Migeotte I, Charles P, Bassi MT, Klopstock T, Mochel F, Ollagnon-Roman E, D'Hooghe M, Kamm C, Kurzwelly D, Papin M, Davoine CS, Banneau G, Tezenas du Montcel S, Seilhean D, Brice A, Duyckaerts C, Stevanin G, Durr A. Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7. Neurology. 2019 Jun 4;92(23):e2679-e2690. Epub 2019 May 8.


Meeter LHH, Steketee RME, Salkovic D, Vos ME, Grossman M, McMillan CT, Irwin DJ, Boxer AL, Rojas JC, Olney NT, Karydas A, Miller BL, Pijnenburg YAL, Barkhof F, Sánchez-Valle R, Lladó A, Borrego-Ecija S, Diehl-Schmid J, Grimmer T, Goldhardt O, Santillo AF, Hansson O, Vestberg S, Borroni B, Padovani A, Galimberti D, Scarpini E, Rohrer JD, Woollacott IOC, Synofzik M, Wilke C, de Mendonca A, Vandenberghe R, Benussi L, Ghidoni R, Binetti G, Niessen WJ, Papma JM, Seelaar H, Jiskoot LC, de Jong FJ, Donker Kaat L, Del Campo M, Teunissen CE, Bron EE, Van den Berg E, Van Swieten JC. Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia. J Neurol Neurosurg Psychiatry. 2019 May 23. pii: jnnp-2018-319784. doi: 10.1136/jnnp-2018-319784. [Epub ahead of print]


Dogan I, Romanzetti S, Didszun C, Mirzazade S, Timmann D, Saft C, Schöls L, Synofzik M, Giordano IA, Klockgether T, Schulz JB, Reetz K. Structural characteristics of the central nervous system in Friedreich ataxia: an in vivo spinal cord and brain MRI study. J Neurol Neurosurg Psychiatry. 2019 May;90(5):615-617. Epub 2018 Jun 26.



Wilke C, Baets J, De Bleecker JL, Deconinck T, Biskup S, Hayer SN, Zuchner S, Schule R, De Jonghe P, Synofzik M. Beyond ALS and FTD: the phenotypic spectrum of TBK1 mutations includes PSP-like and cerebellar phenotypes. Neurobiology of Aging 62:244 e249-244


Roeben B, Schule R, Ruf S, Bender B, Alhaddad B, Benkert T, Meitinger T, Reich S, Bohringer J, Langhans CD, Vaz FM, Wortmann SB, Marquardt T, Haack TB, Krageloh-Mann I, Schols L, Synofzik M  SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family. Journal of Medical Genetics 55:39-47


Wilke C, Bender F, Hayer SN, Brockmann K, Schols L, Kuhle J, Synofzik M. Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. Journal of Neurology 265:1618-1624


Vogel AP, Rommel N, Oettinger A, Stoll LH, Kraus EM, Gagnon C, Horger M, Krumm P, Timmann D, Storey E, Schols L, Synofzik M. Coordination and timing deficits in speech and swallowing in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Journal of Neurology, 2018 May 21;5(7):876-882


Dogan I, Romanzetti S, Didszun C, Mirzazade S, Timmann D, Saft C, Schols L, Synofzik M, Giordano IA, Klockgether T, Schulz JB, Reetz K. Structural characteristics of the central nervous system in Friedreich ataxia: an in vivo spinal cord and brain MRI study. Journal of Neurology Neurosurgery and Psychiatry; Epub ahead of print


Synofzik M, Helbig KL, Harmuth F, Deconinck T, Tanpaiboon P, Sun B, Guo W, Wang R, Palmaer E, Tang S, Schaefer GB, Gburek-Augustat J, Zuchner S, Krageloh-Mann I, Baets J, de Jonghe P, Bauer P, Chen SRW, Schols L, Schule R. De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function. European Journal of Human Genetics; Epub ahead of print


Baradaran-Heravi Y, Dillen L, Nguyen HP, Van Mossevelde S, Baets J, De Jonghe P, Engelborghs S, De Deyn PP, Vandenbulcke M, Vandenberghe R, Van Damme P, Cras P, Salmon E, Synofzik M, Heutink P, Wilke C, Simon-Sanchez J, [….], Van Broeckhoven C, van der Zee J, Consortium B, Consortium EE. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients. Neurobiology of Aging 69:293 e299-293 e211


Lessard I, Brais B, Cote I, Lavoie C, Synofzik M, Mathieu J, Gagnon C. Assessing mobility and balance in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay population: Validity and reliability of four outcome measures. Journal of the Neurological Sciences 390:4-9


Wilke C, Rattay TW, Hengel H, Zimmermann M, Brockmann K, Schols L, Kuhle J, Schule R, Synofzik M. Serum neurofilament light chain is increased in hereditary spastic paraplegias. Annals of  Clinical and Translational Neurology 5:876-882


Pottier C, Zhou X, Perkerson RB, 3rd, Baker M, Jenkins GD, Serie DJ, Ghidoni R, Benussi L, Binetti G, Lopez de Munain A, Zulaica M, Moreno F, Le Ber I, Pasquier F, Hannequin D, Sanchez-Valle R, Antonell A, Llado A, Parsons TM, Finch NA, Finger EC, Lippa CF, Huey ED, Neumann M, Heutink P, Synofzik M, Wilke C, […], Borroni B, Rossi G, Tagliavini F, Wszolek ZK, Petersen RC, Bigio EH, Grossman M, Van Deerlin VM, Seeley WW, Miller BL, Graff-Radford NR, Boeve BF, Dickson DW, Biernacka JM, Rademakers R. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558


Schuster S, Schelling Y, Synofzik M, Hoflinger P, Schols L, Hauser S. Establishment of STUB1/CHIP mutant induced pluripotent stem cells (iPSCs) from a patient with Gordon Holmes syndrome/SCAR16. Stem cell research 29:166-169


Porpora M, Sauchella S, Rinaldi L, Delle Donne R, Sepe M, Torres-Quesada O, Intartaglia D, Garbi C, Insabato L, Santoriello M, Bachmann VA, Synofzik M, Lindner HH, Conte I, Stefan E, Feliciello A. Counterregulation of cAMP-directed kinase activities controls ciliogenesis. Nature Communications 9:1224


Rosenbohm A, Liu M, Nagel G, Peter RS, Cui B, Li X, Kassubek J, Rothenbacher D, Lule D, Cui L, , [study group: Synofzik M.], Ludolph AC, Group ALSRSS. Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany. Journal of Neurology 265:774-782


Rosenbohm A, Nagel G, Peter RS, Brehme T, Koenig W, Dupuis L, Rothenbacher D, [study group: Synofzik M.],  Ludolph AC, Group ALSRS. Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis. JAMA Neurology 75:600-607


Gagnon C, Lessard I, Brais B, Cote I, Lavoie C, Synofzik M, Mathieu J. Validity and Reliability of Outcome Measures Assessing Dexterity, Coordination, and Upper Limb Strength in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. Arch Phys Med Rehabil; Sep;99(9):1747-1754


Kraus EM, Rommel N, Stoll LH, Oettinger A, Vogel AP, Synofzik M. Validation and Psychometric. Properties of the German Version of the SWAL-QOL. Dysphagia 33:431-440


Blauwendraat C, Wilke C, Simon-Sanchez J, [….], Biskup S, Maetzler W, Rizzu P, Heutink P, Synofzik M. The wide genetic landscape of clinical frontotemporal dementia: systematic combined sequencing of 121 consecutive subjects. Genetics in Medicine:E2018 Feb;20(2):240-249


Rattay TW, Just J, Röben B, Hengel H, Schüle R, Synofzik M, Söhn AS, Winter N, Dammeier N, Schöls L, Grimm A. Nerve ultrasound characterizes AMN polyneuropathy as inhomogeneous and focal hypertrophic. Orphanet J Rare Dis. 2018 Nov 3;13(1):194.


Traschütz A, van Gaalen J, Oosterloo M, Vreeburg M, Kamsteeg EJ, Deininger N, Rieß O, Reimold M, Haack T, Schöls L, van de Warrenburg BP, Synofzik M. The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature. Parkinsonism Relat Disord. 2018 Nov 29. pii: S1353-8020(18)30524-8. [Epub ahead of print]


Fleszar Z, Mellone S, Giese M, Tacconi C, Becker C, Schöls L, Synofzik M, Ilg W. Real-time use of audio-biofeedback can improve postural sway in patients with degenerative ataxia. Ann Clin Transl Neurol. 2018 Nov 28;6(2):285-294. eCollection 2019 Feb.



Wilke C, Gillardon F, […], Gasser T, Maetzler W, Blauwendraat C, Synofzik M. Cerebrospinal Fluid Progranulin, but Not Serum Progranulin, Is Reduced in GRN-Negative Frontotemporal Dementia. Neurodegenerative Diseases 17:83-88.


van der Zee J, Gijselinck I, [….], Synofzik M, Just J, Schöls L, […], Fraidakis MJ, Kovacs GG, Fabrizi GM, Testi S.  TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. Human Mutation 38:297-309


Estrada-Cuzcano A, Martin, S., Chamova, T., Synofzik, M., Timmann, D.,[….],Tournev, I., Schule, R. Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78). Brain 140:287-305


Hayer SN, Deconinck T, Bender B, Smets K, Zuchner S, Reich S, Schols L, Schule R, De Jonghe P, Baets J, Synofzik M. STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations. Orphanet Journal of Rare Diseases 12:31


Minnerop M, Kurzwelly, D, Wagner H, […], Hengel H, Synofzik M, Atasu B, Feely S., [….] Ramirez A, Schüle R. Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. Brain 140: 1561-1578


Bis DM, Schüle R, Reichbauer J, Synofzik M, Rattay T, Söhn A, De Jonghe P, Schöls L, Züchner S. Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias. Molecular Genetics & Genomic Medicine 5: 280-286


Ozes B, Karagoz N, Schüle R, Harmuth F, Rebelo A, Sobrido M-J, Synofzik M, […], Battaloglu E. PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia. Clinical Genetics 92: 534-539


Vogel AP, Wardrop MI, Folker JE, Synofzik M, Corben LA, Delatycki MB, Awan SN. Voice in Friedreich Ataxia. Journal of Voice 31: 243


Holler M, Ehricke HH, Synofzik M, Klose U, Groeschel S. Clinical Application of Fiber Visualization with LIC Maps Using Multidirectional Anisotropic Glyph Samples (A-Glyph LIC). Clinical Neuroradiology 27:263-273


Schatton C*, Synofzik M*, Fleszar Z, Giese MA, Schöls L, Ilg W. Individualized exergame training improves postural control in advanced degenerative spinocerebellar ataxia:  a rater-blinded, intra-individually controlled trial. Parkinsonism & Related Disorders 39: 80-84


Vogel AP, Rommel N, Sauer C, Horger M, Krumm P, Himmelbach M, Synofzik M. Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment. Journal of Neurology 264:1107-1117.


Vogel AP, Rommel N, Oettinger A, Horger M, Krumm P, Kraus EM, Schols L, Synofzik M. Speech and swallowing abnormalities in adults with POLG associated ataxia (POLG-A). Mitochondrion 37:1-7


Fomina T, Weichwald S, Synofzik M, Just J, Schols L, Scholkopf B, Grosse-Wentrup M. Absence of EEG correlates of self-referential processing depth in ALS. PloS One 12:e0180136


Blauwendraat C, Wilke C, Simon-Sanchez J, [….], Biskup S, Maetzler W, Rizzu P, Heutink P, Synofzik M. The wide genetic landscape of clinical frontotemporal dementia: systematic combined sequencing of 121 consecutive subjects. Genetics in Medicine: Epub ahead of print


Giordano I, Harmuth F, Jacobi H, Paap B, Vielhaber S, Machts J, Schols, L, Synofzik M, Sturm M,  Tallaksen C. […], Tezenas du Montcel S, Klockgether T. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. Neurology 89:1043-1049


Pham MH, Elshehabi M, Haertner L, Del Din S, Srulijes K, Heger T, Synofzik M, [….], Schmidt G, Maetzler W. Validation of a Step Detection Algorithm during Straight Walking and Turning in Patients with Parkinson's Disease and Older Adults Using an Inertial Measurement Unit at the Lower Back. Frontiers in Neurology 8:457.


Masnada S, Hedrich UBS, Gardella E, Schubert J, Kaiwar C, Klee EW, Lanpher BC, Gavrilova, RH, Synofzik M, [….], Lemke JR, Moller RS, Lerche H, Rubboli G. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies. Brain 140:2337-2354


Renaud M, Tranchant C, Martin JVT, Mochel F, Synofzik M, van de Warrenburg B, Pandolfo M, Koenig M, Kolb SA, Anheim M, Radial Working Group. A recessive ataxia diagnosis algorithm for the next generation sequencing era. Annals of Neurology 82:892-899.


Marquetand J, Knake S, Strzelczyk A, Steinhoff BJ, Lerche H, Synofzik M, Focke NK. Periodic EEG patterns in sporadic Creutzfeld-Jakob-Disease can be benzodiazepine-responsive and be difficult to distinguish from non-convulsive status epilepticus. Seizure 53:47-50.


Maas RR, Iwanicka-Pronicka K, Kalkan Ucar S, Alhaddad B. [….], Synofzik M,  [….], Pronicka E., Wevers RA, de Brouwer AP, Wortmann SB. Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases. Annals of Neurology 82:1004-1015.


Hohmann MR, Fomina T, Jayaram V, Emde T, Just J, Synofzik M, Scholkopf B, Schols L, Grosse-Wentrup M. Case series: Slowing alpha rhythm in late-stage ALS patients. Clinical Neurophysiology 129:406-408.



Blauwendraat C, Wilke C, Jansen IE, […], Rizzu P, Heutink P, Synofzik M. Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiology of Aging 37:208 e211-207


Pilotto A, Schulte C, […], Synofzik M, Maetzler W, Suenkel U, Srulijes K, Gasser T, Berg D. GBA-associated parkinsonism and dementia: beyond alpha-synucleinopathies? European Journal of Neurology 23:520-526.


Wilke C, Pomper JK, Biskup S, Puskas C, Berg D, Synofzik M. Atypical parkinsonism in C9orf72 expansions: a case report and systematic review of 45 cases from the literature. J Neurol 263:558-574.


Keskin I, Forsgren E, Lange DJ, Weber M, Birve A, Synofzik M, Gilthorpe JD, Andersen PM, Marklund SL. Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients. PloS One 11:e0150133


Wilke C, Gillardon F, […], Heutink P, Maetzler W, Synofzik M. Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease. Curr Alzheimer Res 13:654-662


Mademan I, Harmuth F, […], Baets J, Synofzik M. Multisystemic SYNE1 ataxia: confirming the high frequency and extending the mutational and phenotypic spectrum. BRAIN 139:8:e46.


Synofzik M, Smets K, Mallaret M, […], Schule R, de Jonghe P, Anheim M, Taroni F, and Bauer P. SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. BRAIN 139: 1378-1393.


Klenk J, Srulijes K, Schatton C, Schwickert L, Maetzler W, Becker C, Synofzik M. Ambulatory Activity Components Deteriorate Differently across Neurodegenerative Diseases: A Cross-Sectional Sensor-Based Study. Neurodegenerative Diseases 16:317-323.


Wilke C, Preische O, Deuschle C, Roeben B, Apel A, Barro C, Maia L, Maetzler W, Kuhle J, Synofzik M. Neurofilament light chain in FTD is elevated not only in cerebrospinal fluid, but also in serum. J Neurol Neurosurg Psychiatry 87:1270-1272.


Synofzik M, Fleszar Z, Schols L, Just J, Bauer P, Torres Martin JV, Kolb S. Identifying Niemann-Pick type C in early-onset ataxia: two quick clinical screening tools. Journal of Neurology 263:1911-1918.


Helbig KL Hedrich UB, […] Synofzik M, […], Helbig I, Lerche H, Lemke JR. A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia. Annals of Neurology, 80 (4)


Hohmann MR, Fomina T, […], Synofzik M, Scholkopf B, Schols L, Grosse-Wentrup M. A cognitive brain-computer interface for patients with amyotrophic lateral sclerosis. Prog Brain Res 228:221-239.


Kruger S, Battke F, Sprecher A, Munz M, Synofzik M, Schols L, Gasser T, Grehl T, Prudlo J, Biskup S. Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort. Frontiers in Molecular Neuroscience 9:92.


Ilg W, Fleszar Z, Schatton C, Hengel H, Harmuth F, Bauer P, Timmann D, Giese M, Schols L, Synofzik M. Individual changes in preclinical spinocerebellar ataxia identified via increased motor complexity. Mov Disord 31:1891-1900.


Bonifert T, Gonzalez Menendez I, Battke F, Theurer Y, Synofzik M, Schols L, Wissinger B. Antisense Oligonucleotide Mediated Splice Correction of a Deep Intronic Mutation in OPA1. Molecular Therapy - Nucleic Acids 5:e390.


Hauser S, Schuster S, Theurer Y, Synofzik M, Schols L. Generation of optic atrophy 1 patient-derived induced pluripotent stem cells (iPS-OPA1-BEHR) for disease modeling of complex optic atrophy syndromes (Behr syndrome).Stem Cell Research 17:426-429.


Metzger FG, Schopp B, Haeussinger FB, Dehnen K, Synofzik M, Fallgatter AJ, Ehlis AC. Brain activation in frontotemporal and Alzheimer's dementia: a functional near-infrared spectroscopy study. Alzheimers Research & Therapy 8:56



Brendel B, Synofzik M, Ackermann H, Lindig T, Scholderle T, Schols L, Ziegler W. Comparing speech characteristics in spinocerebellar ataxias type 3 and type 6 with Friedreich ataxia. Journal of Neurology 262:21-26


Tarnutzer AA, Gerth-Kahlert C, Timmann D, Chang DI, Harmuth F, Bauer P, Straumann D, Synofzik M. Boucher-Neuhauser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature. Journal of Neurology 262:194-202


Gentsch A, Weiss C, Spengler S, Synofzik M, Schutz-Bosbach S. Doing good or bad: How interactions between action and emotion expectations shape the sense of agency. Social neuroscience:1-13; epub ahead of print


Wilke C, Deuschle C, Rattay TW, Maetzler W, Synofzik M. Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis. Neurobiology of Aging 36:1072-1074.


Obayashi M, Stevanin G, Synofzik M, […], Durr A. Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion. J Neurol Neurosurg Psychiatry 86:986-995.


Syrbe S, Hedrich UB, Riesch E. […] Synofzik M, […], Lerche H, Lemke J.R. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nature Genetics 47:393-399



Smets K, Duarri A, Deconinck T, Ceulemans B, van de Warrenburg BP, Zuchner S, Gonzalez MA, Schule R, Synofzik M, De Jonghe P, Verbeek DS, Baets J. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy. BMC Medical Genetics 16:51


Sultana S, Reichbauer J, Schule R, Mochel F, Synofzik M, van der Spoel AC. Lack of enzyme activity in GBA2 mutants associated with hereditary spastic paraplegia/cerebellar ataxia (SPG46). Biochemical and Biophysical Research Communications 465:35-40.


Strickland AV, Schabhuttl M, Offenbacher H, Synofzik M, […], Schule R, Shy ME, Auer-Grumbach M. Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1. Journal of Neurology 262:2124-2134


Synofzik M, Harmuth F, Stampfer M, Muller Vom Hagen J, Schols L, Bauer P. NPC1 is enriched in unexplained early onset ataxia: a targeted high-throughput screening. Journal of Neurology 262:2557-2563.



Heni M, Schopfer P, […], Synofzik M, Haring HU, Maetzler W, Hennige AM. Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans. Acta diabetologica 51:679-681


Synofzik M*, Gonzalez MA*, Lourenco CM*, Coutelier M, […] Marques W, Jr., Zuchner S. PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. BRAIN 137:69-77.


Mallaret M*, Synofzik M*, Lee J, […] Schüle R, Schöls L, Aldaz M, Koenig M. The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation. BRAIN. 137:411-419.


Synofzik M, Muller Vom Hagen J, Haack TB, Wilhelm C, Lindig T, Beck-Wodl S, Nabuurs SB, van Kuilenburg AB, de Brouwer AP, Schols L. X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation. Orphanet Journal of Rare Diseases 9:24


Synofzik M, Schule R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, Krageloh-Mann I, Gonzalez M, Young P, Zuchner S, Schols L, Bauer P. Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic  paraplegia cohorts. Orphanet Journal of Rare Diseases 9:57.


van der Zee J, Van Langenhove T, [...], Synofzik M, […], Cruts M, Sleegers K, and Van Broeckhoven C. Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration. Acta neuropathologica 2014; 128:397-410.


Bonifert T, Karle KN, […], Schols L, Wissinger B, Synofzik M. Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier. Brain 137:2164-2177


Synofzik M*, Haack TB*, Kopajtich R*, Gorza M, […], Schols L, Prokisch H. Absence of BiP Co-chaperone DNAJC3 Causes Diabetes Mellitus and Multisystemic Neurodegeneration. American Journal of Human Genetics 95:689-697.


Doss S, Wandinger, KP, Hyman, BT, Panzer JA, Synofzik M, Dickerson B, […], Komorowski L, Stocker W, Dalmau J, Pruss H. High Prevalence of NMDA Receptor IgA/IgM Antibodies in Different Dementia Types. Ann Clin Transl Neurol 1: 822-32.



Fischer MD, Synofzik M, Kernstock C, Dietzsch J, Heidlauf R, Schicks J, Srulijes K, Wiethoff S, Menn O, Berg D. Decreased retinal sensitivity and loss of retinal nerve fibers in multiple system atrophy . Graefe's archive for clinical and experimental ophthalmology 251:235-241


van der Zee J*, Gijselinck I*, [...], Synofzik M, […], Van Broeckhoven C (* contributed equally). A Pan-European study of the C9orf72 Repeat Associated with FTLD: Geographic Prevalence, Genomic Instability and Intermediate Repeats. Hum Mutat 34(2): 363-373


Wilke C, Synofzik M, Lindner A. Sensorimotor recalibration depends on attribution of sensory prediction errors to internal causes. PloS one 8:e54925


Brendel B, Ackermann H, Berg D, Lindig T, Scholderle T, Schols L, Synofzik M, Ziegler W. Friedreich ataxia: dysarthria profile and clinical data. Cerebellum 12:475-484


Daoud H, […], Synofzik M, […], Bernard G. Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. J Med Genet 50:194-197


Schicks J, Muller Vom Hagen J, Bauer P, Beck-Wodl S, Biskup S, Krageloh-Mann I, Schols L, Synofzik M. Niemann-Pick type C is frequent in adult ataxia with cognitive decline and vertical gaze palsy. Neurology 80:1169-1170


Synofzik M, […], Schols L. Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum. Orphanet journal of rare diseases 8:41.


Roth MJ, Synofzik M, Lindner A. The Cerebellum Optimizes Perceptual Predictions about External Sensory Events. Curr Biol 23:930-935


Borchers S, Müller L, Synofzik M, Himmelbach M. Guidelines and quality measures for the diagnosis of optic ataxia. Frontiers in human neuroscience 7:324.


Giordano I, Bogdanow M, Jacobi H, Jahn K, Minnerop M, Schoels L, Synofzik M, Teufel J, Klockgether T. Experience in a short-term trial with 4-Aminopyridine in cerebellar ataxia. Journal of Neurology 260:2175-2176


Muller Vom Hagen J, Synofzik M, Schicks J, Krageloh-Mann I, Schols L. Leukodystrophies in idiopathic adult-onset ataxia: frequency and phenotype in 105 patients. Mov Disord 28:2033-2035


Borchers S, Synofzik M, Kiely E, Himmelbach M. Routine Clinical Testing Underestimates Proprioceptive Deficits in Friedreich's Ataxia. Cerebellum 12:916-922


Krieger M, […], Synofzik M, […], Zerres K, Weis J, Senderek J. SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome. Brain 136:3634-3644

All outpatient clinics at a glance



Ataxia Outpatient Clinic


This outpatient clinic is highly specialized on examining and treating patients with degenerative diseases of the cerebellum (cerebellar ataxia) and its afferent tracts (afferent ataxia). It is guided by the goal to provide each patient with an exact molecular diagnosis and, if possible, with an individualized treatment regime.

For office hours, contact persons and further information please see the homepage of the Ataxia Outpatient Clinic, Center for Neurology, University Hospital Tübingen.


Outpatient Clinic for Frontotemporal Dementias and Early Onset Dementias

 The FTD/EOD outpatient clinic has profound expertise in examining patients with Frontotemporal Dementia (FTD), FTD-spectrum diseases (ALS-FTD, frontal variant PSP, CBS), FTD mimics (frontal variant Alzheimer Disease), and other Early-Onset Dementias (dementia onset <  age 65years). It aims to deliver an exact dementia diagnosis, to unravel the causes of the dementia process and its contributing factors, and to provide an individualized counselling and treatment regime.

For office hours, contact persons and further information please see the homepage of the Outpatient Clinic for Frontotemporal Demetia and Early-Onset Dementias, Center of Neurology, University Hospital Tübingen.


Outpatient Clinic for Amyotrophic Lateral Sclerosis

The ALS outpatient clinic examines patients with Amyotrophic Lateral Sclerosis (ALS) or other degenerative motor neuron diseases. It aims to deliver an exact individual diagnosis and to provide an individually tailored counselling and treatment.

For office hours, contact person and further information please see the homepage of the Outpatient Clinic for Amyotrophic Lateral Sclerosis, Center of Neurology, University Hospital Tübingen.

Research Group Leader
Prof. Dr. Matthis Synofzik Address

Center of Neurology
Hertie Institute for Clinical Brain Research
Department Neurodegenerative Diseases

Hoppe-Seyler-Straße 3
72076 Tübingen

Phone: +49 (0)7071 29-82060