Department of Neurodegenerative Disorders

 

Department of Neurodegenerative Disorders

 

Department of Neurodegenerative Disorders headed by prof. Maria Barcikowska was established as an independent unit in 2000. The research scope of the Department encompass diagnosis, treatment of the vast spectrum of neurodegenerative disorders, as well as the basic research in the field of genomics, transcriptomics, biochemistry and cell biology. The Department is a center of differential diagnosis of Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), frontotemporal dementia (FTD), Lewy body dementia (LBD), vascular dementia (VD), and other older age neurodgenerative conditions.

Two closely co-operating units form the Department: Alzheimer's Disease Division of the Clinic of Neurology, localized in the Central Clinical Hospital of the Ministry of Internal Affairs and Administration (head: prof. Tomasz Gabryelewicz MD, PhD, DSc) and Laboratory of Neurogenetics (head: prof. Cezary Żekanowski PhD, DSc), localized in the main MRC building.

 

 

            Alzheimer's Disease Division

Alzheimer's Disease Division is an interdisciplinary unit including specialists in various fields of medicine: neurologists, psychiatrists, neuro-psychologists and psychotherapists. The Division conducts differential diagnosis and treatment of neurodegenerative diseases of the central nervous system and is a part of European Alzheimer’s Disease Consortium (EADC). A biobank of cerebrospinal fluid and DNA samples, as well as cell cultures from the patients diagnosed in the Division is the basis for diagnosis and research. BIOMARKAPD (Biomarkers for Alzheimer’s and Parkinson’s disease) program is implemented in the Division.

 

Team (MRC employees):

Head of the Department of Neurodegenerative Disorders and Clinic of Neurology: prof. Maria Barcikowska MD, PhD, DSc  (@: This email address is being protected from spambots. You need JavaScript enabled to view it. )

Head of the Alzheimer's Disease Division: assoc. prof. Tomasz Gabryelewicz MD, PhD, DSc (@: This email address is being protected from spambots. You need JavaScript enabled to view it. )

Anna Barczak MD, PhD @:  This email address is being protected from spambots. You need JavaScript enabled to view it.

Monika Mandecka MD, PhD  @:  This email address is being protected from spambots. You need JavaScript enabled to view it.

Maria Styczyńska MD, PhD  @:  This email address is being protected from spambots. You need JavaScript enabled to view it.

 

secretary: Monika Zawadzka (tel. 22 508 14 20, This email address is being protected from spambots. You need JavaScript enabled to view it. )

 

 

 

Laboratory of Neurogenetics

 

 

Team:

Professor and Head: Cezary Żekanowski PhD, DSc

tel. 22 60 86 485; @: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Beata Pepłońska PhD, DSc @: This email address is being protected from spambots. You need JavaScript enabled to view it.

Katarzyna Gawęda-Walerych PhD @: This email address is being protected from spambots. You need JavaScript enabled to view it.

Michalina Wężyk PhD  @: This email address is being protected from spambots. You need JavaScript enabled to view it.

Mariusz Berdyński PhD @: This email address is being protected from spambots. You need JavaScript enabled to view it.

Jakub P. Fichna PhD @: This email address is being protected from spambots. You need JavaScript enabled to view it.

Małgorzata Kobryś, technician @: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

We are interested in various aspects of molecular basis of neurodegenerative disorders, especially Alzheimer's disease (AD), fronto-temporal dementia (FTD), Parkinsons disease (PD), amyotrophic lateral sclerosis (ALS), and most recently rare muscular disorders (miopathies and dystrophies), Gilles de la Tourette syndrome, and autism. Our major projects focus on the following:

 

Beata Pepłońska PhD:

1.Searching for mutations in neurodegenerative disorders in patients with a single variant of the TREM2 gene. The aim is the search for biallelic variants in the TREM2 gene in FTD, AD and ALS patients with previously characterized rare variants in the exon coding for the receptor domain of the protein. The regions affecting expression of the TREM2 gene are also analyzed and the co-existence of variants in other genes related to neurodegeneration is assessed. Targeted next generation sequencing approach is used.

2. Searching for rare genetic variants in atypical forms of Alzheimer's disease (Corticobasal syndrome and Posterior Cortical Atrophy) using WES.

3. Identification of sport-related genetic variants using WGS and bioinformatics analyses. The study is performed in cooperation with University of Physical Education in Warsaw (prof. Henryk Sozański, prof. Jakub Adamczyk), University of Physical Education and Sport in Gdańsk (prof. Paweł Cięszczyk) and Pomeranian Medical University in Szczecin (prof. Krzysztof Safranow).

4. Analysis of association between variants in genes coding for proteins involved in neurons’ myelination (MYRF and SOX10)  and outstanding sports results and neurodegeneration. The research is perform in cooperation with University of Physical Education in Warsaw (prof. Jakub Adamczyk), University of Physical Education and Sport in Gdańsk (prof. Paweł Cięszczyk) and Laboratory of Molecular Genetics of National Research Institute of Animal Production in Balice (dr Agata Piestrzyńska-Kajtoch).

 

Michalina Wężyk PhD:

1. functional studies of familial AD usingpatient-derived primary cell lines of skin fibroblasts as a model. We perform whole transcriptome profiling RNASeq method followed by advanced bioinformatic analyses of raw data. Then functional studies of selected signaling pathways related to AD pathology (e.g. DNA damage stress response, BRCA1 signaling, cell cycle re-entry) by standard molecular biology and
biochemistry methods) are performed in a collaboration with prof. Urszula Wojda (Laboratory Of Preclinical Testing Of Higher Standard, at the Neurobiology Center, Nencki Institute of Experimental Biology).

2. modeling of AD using patient-derived fibroblasts reprogrammed into induced pluripotent stem (iPS) cells, further induced into neuro-epithelial like stem (NES) cells, and then differentiated into GABAergic and glutamatergic neurons and glial cells, performed in collaboration with prof. Anna Falk, (Reprogramming and Disease Modeling Laboratory, at the Department of Neurobiology, Karolinska Institutet,
Stockholm, Sweden). We use both standard molecular biology and biochemistry methods as well as specialized electrophysiological measurements, or microscopic in vivo imaging of calcium homeostasis.

 

Mariusz Berdyński PhD:

1. Exploring the genetic background of amyotrophic lateral sclerosis (ALS) and verification contribution of ALS related genes mutation in Polish population. Analysis of the biological effects of mutations and novel rare genetic variants, especially those not linked previously to amyotrophic lateral sclerosis (ALS).  The practical aim of the project is to develop a method combining the detection of causative genetic variants with the determination of their functional effect at the level of the cell and the organism and with their impact on clinical phenotype.

 

Jakub P. Fichna PhD:

1. Exploring genomic background of rare neuropsychiatric and muscle disorders. We use whole exome, whole genome seqencing (WES, WGS) or target sequencing methods combined with advanced bioinformatic assessment of identified genomic variants to pinpoint causative and phenotype-modifying genomic variants in Gilles de la Tourette syndrome, autism, limb-girdle muscular dystrophy (LGMD) and myofibrillar myopathy (MFM). We propose that muscle diseases like LGMD and MFM could be oligogenic, rather than monogenic disorders, with multiple phenotype-influencing semi-causative variants. The results obtained with Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE) suggest de novo structural variants as particular risk factors in neuropsychiatric disorders. The studies are performed in collaboration with prof. Piotr Janik (Department of Neurology, Medical University of Warsaw), prof. Peristera Paschou (Department of Biological Sciences, Purdue University, United States), Michał Korostyński PhD (Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences), prof. Sławomir Filipek (Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw), prof. Jolanta Rędowicz (Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences) and prof. Anna Kostera-Pruszczyk(Department of Neurology, Medical University of Warsaw).

 

Katarzyna Gawęda-Walerych, PhD:

1. Analysis of cellular and molecular processes underlying the pathogenesis of Fronto-Temporal Dementias disease spectrum (FTD) caused by PGRN, MAPT and C9orf72 mutations,  with particular interest in mitochondrial function and autophagy. Research carried out in collaboration with Laboratory of Advanced Microscopy Techniques at  MMRC (Hanna Kozlowska, PhD), and neurologists and neuropsychologists from Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw (prof Barcikowska, MD, PhD, Maria Styczyńska, MD, PhD; Monika Madecka, MD, PhD, Anna Barczak, PhD) and St. Adalbert Hospital, Department of Neurological and Psychiatric Nursing, Medical University of Gdansk (Prof. Jarosław Sławek, MD, PhD; Emilia Sitek, PhD; Ewa Narożańska, PhD; Bogna Brockhuis, PhD).

2. Functional analysis of mutations related to neurodegenerative diseases such as Parkinson’s disease, Fronto-Temporal Dementia detected through whole exome/genome sequencing (WES/WGS). The objective is to determine the mRNA/protein levels and in case of splicing-related mutations mRNA /protein isoforms (also in minigene system) arising due to mutations or their relative ratios, followed by characterization of splicing factors (SF) and splicing regulatory elements (SRE). Ultimate goal is to design targeted, personalized therapeutic approaches based on administration of small molecules (e.g. resveratrol, SAHA) or modified U1/U7 snRNAs. The research is a continuation of a 2-year post-doc project carried out in The International Centre for Genetic Engineering and Biotechnology, in Italy (2014-16).

 

Lab gallery

 

Recent publications:

1. Kuźma-Kozakiewicz M, Andersen PM, Elahi E, Alavi A, Sapp PC, Morita M, Żekanowski C, Berdyński M. - Putative founder effect in the Polish, Iranian and United States populations for the L144S SOD1 mutation associated with slowly uniform phenotype of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2020 Aug 10:1-6.

2. Szejko N, Fichna JP, Safranow K, Dziuba T, Żekanowski C, Janik P. - Association of a Variant of CNR1 Gene Encoding Cannabinoid Receptor 1 With Gilles de la Tourette Syndrome. Front Genet. 2020 Mar 4;11:125

3. Jarmula A, Łusakowska A, Fichna JP, Topolewska M, Macias A, Johnson K, Töpf A, Straub V, Rosiak E, Szczepaniak K, Dunin-Horkawicz S, Maruszak A, Kaminska AM, Redowicz MJ. -  ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure. Sci Rep. 2019;9(1):11533.

4. Kieroń M, Żekanowski C, Falk A, Wężyk M - Oxidative DNA Damage Signalling in Neural Stem Cells in Alzheimer's Disease. Oxid Med Cell Longev. 2019 Nov 13;2019:2149812. doi: 10.1155/2019/2149812. eCollection 2019.

5. Hernandez I, Luna G, Rauch JN, Reis SA, Giroux M, Karch CM, Boctor D, Sibih YE, Storm NJ, Diaz A, Kaushik S, Zekanowski C, Kang AA, Hinman CR, Cerovac V, Guzman E, Zhou H, Haggarty SJ, Goate AM, Fisher SK, Cuervo AM, Kosik KS - A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy. Sci Transl Med. 2019 Mar 27;11(485):eaat3005.

6. Peplonska B, Safranow K, Adamczyk J, Boguszewski D, Szymański K, Soltyszewski I, Barczak A, Siewierski M, Ploski R, Sozanski H, Zekanowski C - Association of serotoninergic pathway gene variants with elite athletic status in the Polish population. J Sports Sci. 2019 Jul;37(14):1655-1662.

7. Walerych D, Pruszko M, Zyla L, Wezyk M, Gaweda-Walerych K, Zylicz A - Wild-type p53 oligomerizes more efficiently than p53 hot-spot mutants and overcomes mutant p53 gain-of-function via a "dominant-positive" mechanism. Oncotarget. 2018 Aug 10;9(62):32063-32080. doi: 10.18632/oncotarget.25944. eCollection 2018 Aug 10.

8. Filipek-Gliszczyńska A, Barczak A, Budziszewska M, Mandecka M, Gabryelewicz T, Barcikowska M. - The Erlangen Score Algorithm in the diagnosis and prediction of the progression from subjective cognitive decline and mild cognitive impairment to Alzheimer-type dementia. Folia Neuropathol, 2018, 56:88-96

9. Baranowska-Bik A, Kalisz M, Martyńska L, Wolińska-Witort E, Styczyńska M, Chodakowska-Żebrowska M, Barcikowska M, Baranowska B, Bik W. - Plasma adiponectin array in women with Alzheimer's disease. Endokrynol Pol, 2018, 69: 550-559

10. Bratosiewicz-Wasik J, Liberski PP, Peplonska B, Styczynska M, Smolen-Dzirba J, Cycon M, Wasik TJ. - Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene as risk factors for Alzheimer's disease. Neurosci Lett. 2018, 684: 86-90.

11. Jansen WJ, Ossenkoppele R, Tijms BM, Fagan AM, Hansson O, Klunk WE, van der Flier WM, Villemagne VL, Frisoni GB, Fleisher AS, Lleó A, Mintun MA, Wallin A, Engelborghs S, Na DL, Chételat G, Molinuevo JL, Landau SM, Mattsson N, Kornhuber J, Sabri O, Rowe CC, Parnetti L, Popp J, Fladby T, Jagust WJ, Aalten P, Lee DY, Vandenberghe R, Resende de Oliveira C, Kapaki E, Froelich L, Ivanoiu A, Gabryelewicz T, Verbeek MM, Sanchez-Juan P, Hildebrandt H, Camus V, Zboch M, Brooks DJ, Drzezga A, Rinne JO, Newberg A, de Mendonça A, Sarazin M, Rabinovici GD, Madsen K, Kramberger MG, Nordberg A, Mok V, Mroczko B, Wolk DA, Meyer PT, Tsolaki M, Scheltens P, Verhey FRJ, Visser PJ; Amyloid Biomarker Study Group, Aarsland D, Alcolea D, Alexander M, Almdahl IS, Arnold SE, Baldeiras I, Barthel H, van Berckel BNM, Blennow K, van Buchem MA, Cavedo E, Chen K, Chipi E, Cohen AD, Förster S, Fortea J, Frederiksen KS, Freund-Levi Y, Gkatzima O, Gordon MF, Grimmer T, Hampel H, Hausner L, Hellwig S, Herukka SK, Johannsen P, Klimkowicz-Mrowiec A, Köhler S, Koglin N, van Laere K, de Leon M, Lisetti V, Maier W, Marcusson J, Meulenbroek O, Møllergård HM, Morris JC, Nordlund A, Novak GP, Paraskevas GP, Perera G, Peters O, Ramakers IHGB, Rami L, Rodríguez-Rodríguez E, Roe CM, Rot U, Rüther E, Santana I, Schröder J, Seo SW, Soininen H, Spiru L, Stomrud E, Struyfs H, Teunissen CE, Vos SJB, van Waalwijk van Doorn LJC, Waldemar G, Wallin ÅK, Wiltfang J, Zetterberg H. - Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry, 2018, 75:84-95.

12. Fichna JP, Maruszak A, Żekanowski C. - Myofibrillar myopathy in the genomic context. J Appl Genet. 2018, 59:431-439.

13. Gaweda-Walerych K, Sitek EJ, Narożańska E, Wezyk M, Brockhuis B, Zekanowski C, Sławek J. - Functional characterization of a novel progranulin mutation in a patient with progressive nonfluent aphasia. Neurobiol Aging. 2018 72:186.e9-186.e12.

14. Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C. - Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients. Hum Genomics. 2018, 12: 34.

15. Wezyk M, Spólnicka M, Pośpiech E, Pepłońska B, Zbieć-Piekarska R, Ilkowski J, Styczyńska M, Barczak A, Zboch M, Filipek-Gliszczynska A, Skrzypczak M, Ginalski K, Kabza M, Makałowska I, Barcikowska-Kotowicz M, Branicki W, Żekanowski C. - Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer's Disease. Oxid Med Cell Longev. 2018: 6918797.

16. Wezyk M, Zekanowski C. - Role of BRCA1 in Neuronal Death in Alzheimer's Disease. ACS Chem Neurosci. 2018, 9:870-872.

 17. Peplonska B, Berdynski M, Mandecka M, Barczak A, Kuzma-Kozakiewicz M, Barcikowska M, Zekanowski C. - TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients. Amyotroph Lateral Scler Frontotemporal Degener. 2018, 19:407-412.

18. Spólnicka M, Pośpiech E, Adamczyk JG, Freire-Aradas A, Pepłońska B, Zbieć-Piekarska R, Makowska Ż, Pięta A, Lareu MV, Phillips C, Płoski R, Żekanowski C, Branicki W. - Modified aging of elite athletes revealed by analysis of epigenetic age markers. Aging (Albany NY), 2018, 10:241-252.

19. Wezyk M, Szybinska A, Wojsiat J, Szczerba M, Day K, Ronnholm H, Kele M,Berdynski M, Peplonska B, Fichna JP, Ilkowski J, Styczynska M, Barczak A,Zboch M , Filipek-Gliszczynska A, Bojakowski K, Skrzypczak M, Ginalskii K,Kabza M, Makalowska I, Barcikowska-Kotowicz M, Wojda U, Falk A, Zekanowski  C. - Overactive BRCA1 Affects Presenilin 1 in Induced Pluripotent Stem Cell-Derived Neurons in Alzheimers Disease. Journal of Alzheimers disease. 2018; 62 (1) doi:10.3233/JAD-170830.

20. Keskin I, Birve A, Berdynski M, Hjertkvist K, Rofougaran R, Nilsson TK, Glass JD, Marklund SL, Andersen PM. - Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Aug;18(5-6):457-463.

21. Spólnicka M, Pośpiech E, Pepłońska B, Zbieć-Piekarska R, Makowska Ż, Pięta A, Karłowska-Pik J, Ziemkiewicz B, Wężyk M, Gasperowicz P, Bednarczuk T, Barcikowska M, Żekanowski C, Płoski R, Branicki W. - DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups. Int J Legal Med. 2017 Jul 19. doi: 10.1007/s00414-017-1636-0.

22. Fichna JP, Potulska-Chromik A, Miszta P, Redowicz MJ, Kaminska AM, Zekanowski C, Filipek S. - A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure. BBA Clin. 2016 Nov 11;7:1-7. eCollection 2017 Jun.

23. Herukka SK, Simonsen AH, Andreasen N, Baldeiras I, Bjerke M, Blennow K, Engelborghs S, Frisoni GB, Gabryelewicz T, Galluzzi S, Handels R, Kramberger MG, Kulczyńska A, Molinuevo JL, Mroczko B, Nordberg A, Oliveira CR, Otto M, Rinne JO, Rot U, Saka E, Soininen H, Struyfs H, Suardi S, Visser PJ, Winblad B, Zetterberg H, Waldemar G. - Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment. Alzheimers Dement. 2017 Mar;13(3):285-295. doi:

24. Simonsen AH, Herukka SK, Andreasen N, Baldeiras I, Bjerke M, Blennow K, Engelborghs S, Frisoni GB, Gabryelewicz T, Galluzzi S, Handels R, Kramberger MG, Kulczyńska A, Molinuevo JL, Mroczko B, Nordberg A, Oliveira CR, Otto M, Rinne JO, Rot U, Saka E, Soininen H, Struyfs H, Suardi S, Visser PJ, Winblad B, Zetterberg H, Waldemar G. - Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimers Dement. 2017 Mar;13(3):274-284.

25. Nagaraj S, Laskowska-Kaszub K, Dębski KJ, Wojsiat J, Dąbrowski M, Gabryelewicz T, Kuźnicki J, Wojda U. - Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer's disease patients from non-demented subjects. Oncotarget. 2017 Mar 7;8(10):16122-16143.

26. Markopoulou K, Chase BA, Robowski P, Strongosky A, Narożańska E, Sitek EJ, Berdynski M, Barcikowska M, Baker MC, Rademakers R, Sławek J, Klein C, Hückelheim K, Kasten M, Wszolek ZK. - Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction. PLoS One. 2016 Nov 17;11(11):e0165112. doi: 10.1371/journal.pone.0165112. eCollection 2016.

27. Gaweda-Walerych K, Mohagheghi F, Zekanowski C, Buratti E. - Parkinson's disease-related gene variants influence pre-mRNA splicing processes. Neurobiol Aging. 2016 Jul 28;47:127-138. doi: 10.1016/j.neurobiolaging.2016.07.014.

28. Nesteruk M, Nesteruk T, Styczyńska M, Mandecka M, Barczak A, Barcikowska M. - Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer's disease. Folia Neuropathol. 2016;54(4):369-374.

29. Mandecka M, Budziszewska M, Barczak A, Pepłońska B, Chodakowska-Żebrowska M, Filipek-Gliszczyńska A, Nesteruk M, Styczyńska M, Barcikowska M, Gabryelewicz T. - Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease. J Alzheimers Dis. 2016 Jul 29;54(1):157-68. doi: 10.3233/JAD-160176.

30. Peplonska B, Adamczyk JG, Siewierski M, Safranow K, Maruszak A, Sozanski H, Gajewski AK, Zekanowski C. - Genetic variants associated with physical and mental characteristics of the elite athletes in the Polish population. Scand J Med Sci Sports. 2017 Aug;27(8):788-800. doi: 10.1111/sms.12687. Epub 2016 May 3.

 

Current grants:

1. “Identification and comprehensive characterization of genomic variants associated with Gilles de la Tourette syndrome.” PI: Cezary Żekanowski, National Science Center (NCN) UMO- 2016/23/B/NZ2/03030, 2017 - 2020.

2. „Searching for novel genes determining the predisposition to physical performance” Lider: prof. Paweł Cięszczyk, Partner: prof. Cezary Żekanowski; OPUS14 (NCN) 2017/27/27/B/NZ7/00204,2018 - 2021.