Sektion Molecular Neuropsychiatry

The main focus of our research is the identification of the molecular genetic mechanisms which underlie cognitive disorders including neurodegenerative dementias such as Alzheimer’s disease. To this end, we combine state-of-the-art technologies to discover common and rare genetic variants contributing to both familial and sporadic forms of these disorders. The results of our research are likely to contribute towards the elucidation of the complex genetic architecture of these diseases and the development of novel prevention, diagnostic, therapeutic strategies.

General information to cognitive phenotypes

Cognitive disorders, including Alzheimer’s disease (AD) dementia, are becoming a major public health problem due to rapidly growing prevalence. The etiology of AD is multifactorial which means that susceptibility to the disease results from a complex interaction of genetic, epigenetic and environmental factors. Genetic factors in AD account for up to 80% of the attributable risk (heritability). This strong genetic contribution probably means that genetic determinants are involved in most of the pathophysiological pathways in AD. Thus, the more complete our knowledge on the genetic of AD, the deeper will be our understanding on the fundamental processes occurring in AD. Identification of genetic risk factors for AD began in the early ‘90s with the identification of the apolipoprotein E gene (APOE) as the strongest genetic susceptibility factor for AD. During the last decade, our knowledge of genetic risk factors for AD has been greatly propelled by the development of high throughput genomics, and genome wide association studies (GWAS). These major advancements have allowed, to date, the discovery of more than 20 risk loci for AD besides APOE. However, even though our knowledge of the genetics of AD has progressed markedly over the last few years, it is still far from complete and deciphering the so-called “missing heritability” is one of the main challenges in AD.

Aims of our research

To identify the genetic and epigenetic underpinnings of cognitive disorders, the laboratory of Molecular Neuropsychiatry uses state-of-the-art high-throughput genome technologies in human DNA and RNA samples which are obtained from our own biobank at the Department of Psychiatry or from our several national and international collaborative projects. Thus our research group has access to biomaterials of a sample comprising more than 7000 AD patients, 6000 control samples, and about 9000 mild cognitive impairment (MCI) patients. In addition, in the framework of an international European initiative called EADB, we have access to DNA samples from one of the worldwide largest collections of AD, controls and MCI cases. The genetic and epigenetic data available in these samples allow us to investigate influences of genetic and epigenetic factors in both a genome-wide- and hypothesis-based manner. To this end, score based approaches are applied to the simultaneous consideration of multiple chromosomal loci. We also perform bioinformatics analyses to investigate biological pathways involved in these diseases. Using part of this sample, our group identified a novel genome-wide significant AD susceptibility locus which contains the thyroid receptor interacting protein gene 4 (TRIP4). Our results implicate the thyroid hormone axis among the pathways involved in the susceptibility to AD.

In more recent times, our laboratory initiated a line of research focused on the investigation of genetics in AD progression and cognitive decline at prodromal stages of the disease, such as MCI. Patients with MCI are at increased risk of developing AD dementia. However, the MCI group is heterogeneous, and wide variation in the annual progression rate to AD dementia has been reported, with estimates ranging from 4 to 31%. Thus predicting which MCI cases will actually progress to AD dementia is an important challenge. Given the strong heritability in AD, it is expected that genetic risk factors for AD may also modulate pathophysiological pathways involved in progression of MCI to AD dementia. However, our initial investigations of MCI samples clearly showed that the majority of known genetic risk variants for AD do not predict MCI to dementia progression. Thus, our findings on disease progression in MCI clearly show that most of the genetics modulating progression to AD dementia is still waiting for being discovered.

Publications

h-index: 30 times cited 4,939; * - shared first or last authorship; § - Corresponding author

- Publication 2017

Minnerop M, Kurzwelly D, Wagner H, Soehn AS, Reichbauer J, Tao F, Rattay TW, Peitz M, Rehbach K, Giorgetti A, Pyle A, Thiele H, Altmüller J, Timmann D, Karaca I, Lennarz M, Baets J, Hengel H, Synofzik M, Atasu B, Feely S, Kennerson M, Stendel C, Lindig T, Gonzalez MA, Stirnberg R, Sturm M, Roeske S, Jung J, Bauer P, Lohmann E, Herms S, Heilmann-Heimbach S, Nicholson G, Mahanjah M, Sharkia R, Carloni P, Brüstle O, Klopstock T, Mathews KD, Shy ME, de Jonghe P, Chinnery PF, Horvath R, Kohlhase J, Schmitt I, Wolf M, Greschus S, Amunts K, Maier W, Schöls L, Nürnberg P, Zuchner S, Klockgether T, Ramirez A*,§, Schüle R*. Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. Brain. 2017 Jun 1;140(6):1561-1578. doi: 10.1093/brain/awx095.
Lacour A, Espinosa A, Louwersheimer E, Heilmann S, Hernández I, Wolfsgruber S, Fernández V, Wagner H, Rosende-Roca M, Mauleón A, Moreno-Grau S, Vargas L, Pijnenburg YA, Koene T, Rodríguez-Gómez O, Ortega G, Ruiz S, Holstege H, Sotolongo-Grau O, Kornhuber J, Peters O, Frölich L, Hüll M, Rüther E, Wiltfang J, Scherer M, Riedel-Heller S, Alegret M, Nöthen MM, Scheltens P, Wagner M, Tárraga L, Jessen F, Boada M, Maier W, van der Flier WM, Becker T, Ramirez A*, Ruiz A*. Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment. Mol Psychiatry. 2017 Jan;22(1):153-160. doi: 10.1038/mp.2016.18.

- Publication 2016


Neidhardt G, Hauke J, Ramser J, Groß E, Gehrig A, Müller CR, Kahlert AK, Hackmann K, Honisch E, Niederacher D, Heilmann-Heimbach S, Franke A, Lieb W, Thiele H, Altmüller J, Nürnberg P, Klaschik K, Ernst C, Ditsch N, Jessen F, Ramirez A, Wappenschmidt B, Engel C, Rhiem K, Meindl A, Schmutzler RK, Hahnen E. Association Between Loss-of-Function Mutations Within the FANCM Gene and Early-Onset Familial Breast Cancer. JAMA Oncol. 2016 Dec 29. doi: 10.1001/jamaoncol.2016.5592.
van der Zee J, Gijselinck I, Van Mossevelde S, Perrone F, Dillen L, Heeman B, Bäumer V, Engelborghs S, De Bleecker J, Baets J, Gelpi E, Rojas-García R, Clarimón J, Lleó A, Diehl-Schmid J, Alexopoulos P, Perneczky R, Synofzik M, Just J, Schöls L, Graff C, Thonberg H, Borroni B, Padovani A, Jordanova A, Sarafov S, Tournev I, de Mendonça A, Miltenberger-Miltényi G, Simões do Couto F, Ramirez A, Jessen F, Heneka MT, Gómez-Tortosa E, Danek A, Cras P, Vandenberghe R, De Jonghe P, De Deyn PP, Sleegers K, Cruts M, Van Broeckhoven C, Goeman J, Nuytten D, Smets K, Robberecht W, Damme PV, Bleecker J, Santens P, Dermaut B, Versijpt J, Michotte A, Ivanoiu A, Deryck O, Bergmans B, Delbeck J, Bruyland M, Willems C, Salmon E, Pastor P, Ortega-Cubero S, Benussi L, Ghidoni R, Binetti G, Hernández I, Boada M, Ruiz A, Sorbi S, Nacmias B, Bagnoli S, Sorbi S, Sanchez-Valle R, Llado A, Santana I, Rosário Almeida M, Frisoni GB, Maetzler W, Matej R, Fraidakis MJ, Kovacs GG, Fabrizi GM, Testi S. TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. Hum Mutat. 2016 Dec 23. doi: 10.1002/humu.23161.
Louwersheimer E, Wolfsgruber S, Espinosa A, Lacour A, Heilmann-Heimbach S, Alegret M, Hernández I, Rosende-Roca M, Tárraga L, Boada M, Kornhuber J, Peters O, Frölich L, Hüll M, Rüther E, Wiltfang J, Scherer M, Riedel-Heller S, Jessen F, Nöthen MM, Maier W, Koene T, Scheltens P, Holstege H, Wagner M, Ruiz A, van der Flier WM, Becker T, Ramirez A§. Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment. Alzheimers Dement. 2016 Aug;12(8):872-81. doi: 10.1016/j.jalz.2016.01.006.
Mengel D, Dams J, Ziemek J, Becker J, Balzer-Geldsetzer M, Hilker R, Baudrexel S, Kalbe E, Schmidt N, Witt K, Liepelt-Scarfone I, Gräber S, Petrelli A, Neuser P, Schulte C, Linse K, Storch A, Wittchen HU, Riedel O, Mollenhauer B, Ebentheuer J, Trenkwalder C, Klockgether T, Spottke A, Wüllner U, Schulz JB, Reetz K, Heber IA, Ramirez A, Dodel R. Apolipoprotein E ε4 does not affect cognitive performance in patients with Parkinson's disease. Parkinsonism Relat Disord. 2016 Aug;29:112-6. doi: 10.1016/j.parkreldis.2016.04.013.
Bey K, Wolfsgruber S, Karaca I, Wagner H, Lardenoije R, Becker J, Milz E, Kornhuber J, Peters O, Frölich L, Hüll M, Rüther E, Wiltfang J, Riedel-Heller S, Scherer M, Jessen F, Maier W, van den Hove DL, Rutten BP, Wagner M, Ramirez A§. No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment. Epigenomics. 2016 May;8(5):593-8. doi: 10.2217/epi-2015-0014.
Mengel D, Thelen M, Balzer-Geldsetzer M, Söling C, Bach JP, Schaeffer E, Herold C, Becker T, Liepelt I, Becker J, Riedel-Heller S, Scherer M, Jessen F, Maier W, Dodel R, Ramirez A§. TREM2 rare variant p.R47H is not associated with Parkinson's disease. Parkinsonism Relat Disord. 2016 Feb;23:109-11. doi: 10.1016/j.parkreldis.2015.11.026.
Traylor M, Adib-Samii P, Harold D; Alzheimer's Disease Neuroimaging Initiative.; International Stroke Genetics Consortium (ISGC), UK Young Lacunar Stroke DNA resource., Dichgans M, Williams J, Lewis CM, Markus HS; METASTROKE.; International Genomics of Alzheimer's Project (IGAP) investigators (including Ramirez A). Shared genetic contribution to Ischaemic Stroke and Alzheimer's Disease. Ann Neurol. 2016 Feb 23. doi: 10.1002/ana.24621.
Gusareva ES, Carrasquillo MM, Bellenguez C, Cuyvers E, Colon S, Graff-Radford NR, Petersen RC, Dickson DW, Mahachie John JM, Bessonov K, Van Broeckhoven C; GERAD1 Consortium., Harold D, Williams J, Amouyel P, Sleegers K, Ertekin-Taner N, Lambert JC, Van Steen K, Ramirez A. Genome-wide association interaction analysis for Alzheimer's disease. Neurobiol Aging. 2014 Nov;35(11):2436-43. doi: 10.1016/j.neurobiolaging.2014.05.014. Erratum in: Neurobiol Aging. 2016 Jan;37():211. Ramirez, Alfredo [Added].
Pastor P, Moreno F, Clarimón J, Ruiz A, Combarros O, Calero M, López de Munain A, Bullido MJ, de Pancorbo MM, Carro E, Antonell A, Coto E, Ortega-Cubero S, Hernandez I, Tárraga L, Boada M, Lleó A, Dols-Icardo O, Kulisevsky J, Vázquez-Higuera JL, Infante J, Rábano A, Fernández-Blázquez MÁ, Valentí M, Indakoetxea B, Barandiarán M, Gorostidi A, Frank-García A, Sastre I, Lorenzo E, Pastor MA, Elcoroaristizabal X, Lennarz M, Maier W, Ramirez A, Serrano-Ríos M, Lee SE, Sánchez-Juan P; Dementia Genetic Spanish Consortium (DEGESCO). MAPT H1 Haplotype is Associated with Late-Onset Alzheimer's Disease Risk in APOEɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium. J Alzheimers Dis. 2016;49(2):343-52. doi: 10.3233/JAD-150555.
10. Jun G, Ibrahim-Verbaas CA, Vronskaya M, ……………., Ramirez A, …………….., Amouyel P, Williams J, van Duijn CM, Schellenberg GD, Farrer LA. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry. 2016 Jan;21(1):108-17. doi: 10.1038/mp.2015.23.

- Publication 2015

Escott-Price V, Sims R, Bannister C, Harold D, Vronskaya M, Majounie E, Badarinarayan N; GERAD/PERADES; IGAP consortia, Morgan K, Passmore P, Holmes C, Powell J, Brayne C, Gill M, Mead S, Goate A, Cruchaga C, Lambert JC, van Duijn C, Maier W, Ramirez A, Holmans P, Jones L, Hardy J, Seshadri S, Schellenberg GD, Amouyel P, Williams J. Common polygenic variation enhances risk prediction for Alzheimer's disease. Brain. 2015 Dec;138(Pt 12):3673-84. doi: 10.1093/brain/awv268.
Ramirez A§. Population-Based Genetic Studies: The Search for Causative Variants in Parkinson's Disease. Mov Disord. 2015 Sep;30(10):1297-300. doi: 10.1002/mds.26341. Epub 2015 Jul 30.
Jones L, Lambert JC, Wang LS………….., Ramirez A, Schellenberg GD, Seshadri S, Amouyel P, Williams J, Holmans PA. Convergent genetic and expression data implicate immunity in Alzheimer's disease. Alzheimers Dement. 2015 Jun;11(6):658-71. doi: 10.1016/j.jalz.2014.05.1757. Epub 2014 Dec 20.
Heilmann S, Drichel D, Clarimon J, Fernández V, Lacour A, Wagner H, Thelen M, Hernández I, Fortea J, Alegret M, Blesa R, Mauleón A, Roca MR, Kornhuber J, Peters O, Heun R, Frölich L, Hüll M, Heneka MT, Rüther E, Riedel-Heller S, Scherer M, Wiltfang J, Jessen F, Becker T, Tárraga L, Boada M, Maier W, Lleó A, Ruiz A, Nöthen MM, Ramirez A§. PLD3 in non-familial Alzheimer's disease. Nature. 2015 Apr 2;520(7545):E3-5. doi: 10.1038/nature14039.
Lacour A, Schüller V, Drichel D, Herold C, Jessen F, Leber M, Maier W, Noethen MM, Ramirez A, Vaitsiakhovich T, Becker T. Novel genetic matching methods for handling population stratification in genome-wide association studies. BMC Bioinformatics. 2015 Mar 14;16:84. doi: 10.1186/s12859-015-0521-4.
Louwersheimer E, Ramirez A, Cruchaga C, Becker T, Kornhuber J, Peters O, Heilmann S, Wiltfang J, Jessen F, Visser PJ, Scheltens P, Pijnenburg YA, Teunissen CE, Barkhof F, van Swieten JC, Holstege H, Van der Flier WM; Alzheimer's Disease Neuroimaging Initiative and Dementia Competence Network. The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease. Neurobiol Aging. 2015 Mar;36(3):1605.e13-20. doi: 10.1016/j.neurobiolaging.2014.12.007. Epub 2014 Dec 11.
Ramirez A§, Wolfsgruber S, Lange C, Kaduszkiewicz H, Weyerer S, Werle J, Pentzek M, Fuchs A, Riedel-Heller SG, Luck T, Mösch E, Bickel H, Wiese B, Prokein J, König HH, Brettschneider C, Breteler MM, Maier W, Jessen F, Scherer M; AgeCoDe Study Group. Elevated HbA1c is associated with increased risk of incident dementia in primary care patients. J Alzheimers Dis. 2015;44(4):1203-12. doi: 10.3233/JAD-141521.

- Publication 2014

1      Ramirez A§, Wolfsgruber S, Lange C, Kaduszkiewicz H, Weyerer S, Werle J, Pentzek M, Fuchs A, Riedel-Heller SG, Luck T, Mösch E, Bickel H, Wiese B, Prokein J, König HH, Brettschneider C, Breteler MM, Maier W, Jessen F, Scherer M; AgeCoDe Study Group. Elevated HbA1c is associated with increased risk of incident dementia in primary care patients. J Alzheimers Dis. 2015;44(4):1203-12. doi: 10.3233/JAD-141521.

2      Ramirez A§, van der Flier WM, Herold C, Ramonet D, Heilmann S, Lewczuk P, Popp J, Lacour A, Drichel D, Louwersheimer E, Kummer MP, Cruchaga C, Hoffmann P, Teunissen C, Holstege H, Kornhuber J, Peters O, Naj AC, Chouraki V, Bellenguez C, Gerrish A; International Genomics of Alzheimer's Project (IGAP); Alzheimer's Disease Neuroimaging Initiative (ADNI), Heun R, Frölich L, Hüll M, Buscemi L, Herms S, Kölsch H, Scheltens P, Breteler MM, Rüther E, Wiltfang J, Goate A, Jessen F, Maier W, Heneka MT, Becker T, Nöthen MM. SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease. Hum Mol Genet. 2014 Dec 15;23(24):6644-58. doi: 10.1093/hmg/ddu372.

3      Drichel D, Herold C, Lacour A, Ramirez A, Jessen F, Maier W, Noethen MM, Leber M, Vaitsiakhovich T, Becker T. Rare Variant Testing of Imputed Data: An Analysis Pipeline Typified. Hum Hered. 2014 Dec 10;78(3-4):164-178.

4      Thelen M, Razquin C, Hernández I, Gorostidi A, Sánchez-Valle R, Ortega-Cubero S, Wolfsgruber S, Drichel D, Fliessbach K, Duenkel T, Damian M, Heilmann S, Slotosch A, Lennarz M, Seijo-Martínez M, Rene R, Kornhuber J, Peters O, Luckhaus C, Jahn H, Hüll M, Rüther E, Wiltfang J, Lorenzo E, Gascon J, Lleó A, Lladó A, Campdelacreu J, Moreno F, Ahmadzadehfar H; Dementia Genetics Spanish Consortium (DEGESCO), Fortea J, Indakoetxea B, Heneka MT, Wetter A, Pastor MA, Riverol M, Becker T, Frölich L, Tárraga L, Boada M, Wagner M, Jessen F, Maier W, Clarimón J, López de Munain A, Ruiz A, Pastor P, Ramirez A§. Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes. Neurobiol Aging. 2014 Nov;35(11):2657.e13-9. doi: 10.1016/j.neurobiolaging.2014.06.018.

5      Hooli BV, Parrado AR, Mullin K, Yip WK, Liu T, Roehr JT, Qiao D, Jessen F, Peters O, Becker T, Ramirez A, Lange C, Bertram L, Tanzi RE. The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk. Neurology. 2014 Oct 7;83(15):1353-8. doi: 10.1212/WNL.0000000000000855.

6      Morgen K*, Ramirez A*, Frölich L, Tost H, Plichta MM, Kölsch H, Rakebrandt F, Rienhoff O, Jessen F, Peters O, Jahn H, Luckhaus C, Hüll M, Gertz HJ, Schröder J, Hampel H, Teipel SJ, Pantel J, Heuser I, Wiltfang J, Rüther E, Kornhuber J, Maier W, Meyer-Lindenberg A. Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease. Alzheimers Dement. 2014 Oct;10(5 Suppl):S269-76. doi: 10.1016/j.

7      Escott-Price V, Bellenguez C, Wang LS, ……….., Ramirez A, Seshadri S, Schellenberg GD, Amouyel P, Williams J. Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease. PLoS One. 2014 Jun 12;9(6):e94661. doi: 10.1371/journal.pone.0094661. eCollection 2014.

8      Kaut O, Ramirez A, Pieper H, Schmitt I, Jessen F, Wüllner U. DNA Methylation of the TNF-α Promoter Region in Peripheral Blood Monocytes and the Cortex of Human Alzheimer's Disease Patients. Dement Geriatr Cogn Disord. 2014 Feb 19;38(1-2):10-15. [Epub ahead of print] (http://www.ncbi.nlm.nih.gov/pubmed/24556805)

9      Ruiz A, Heilmann S, Becker T, Hernández I, Wagner H, Thelen M, Mauleón A, Rosende-Roca M, Bellenguez C, Bis JC, Harold D, Gerrish A, Sims R, Sotolongo-Grau O, Espinosa A, Alegret M, Arrieta JL, Lacour A, Leber M, Becker J, Lafuente A, Ruiz S, Vargas L, Rodríguez O, Ortega G, Dominguez MA, IGAP, Mayeux R, Haines JL, Pericak-Vance MA, Farrer LA, Schellenberg GD, Chouraki V, Launer LJ, van Duijn C, Seshadri S, Antúnez C, Breteler MM, Serrano-Ríos M, Jessen F, Tárraga L, Nöthen MM, Maier W, Boada M, Ramírez A§. Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene. Transl Psychiatry. 2014 Feb 4;4:e358. doi: 10.1038/tp.2014.2.(http://www.ncbi.nlm.nih.gov/pubmed/24495969)

10   Doss S, Lohmann K, Seibler P, Arns B, Klopstock T, Zühlke C, Freimann K, Winkler S, Lohnau T, Drungowski M, Nürnberg P, Wiegers K, Lohmann E, Naz S, Kasten M, Bohner G, Ramirez A, Endres M, Klein C. Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation. J Neurol. 2014 Jan;261(1):207-12. doi: 10.1007/s00415-013-7177-7.

- Publication 2013

1      Lambert JC, Ibrahim-Verbaas CA, ……, Ramirez A, …….., Seshadri S, Williams J, Schellenberg GD, Amouyel P. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013 Dec;45(12):1452-8. doi: 10.1038/ng.2802. Epub 2013 Oct 27.

2      Herold C, Ramirez A, Drichel D, Lacour A, Vaitsiakhovich T, Nöthen MM, Jessen F, Maier W, Becker T. A One-Degree-of-Freedom Test for Supra-Multiplicativity of SNP Effects. PLoS One. 2013 Oct 30;8(10):e78038. doi: 10.1371/journal.pone.0078038.

3      de Souza Silva MA, Lenz B, Rotter A, Biermann T, Peters O, Ramirez A, Jessen F, Maier W, Hüll M, Schröder J, Frölich L, Teipel S, Gruber O, Kornhuber J, Huston JP, Müller CP, Schäble S. Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15097-102. doi: 10.1073/pnas.1306884110. Epub 2013 Aug 27.

4      Zou F, Belbin O, Carrasquillo MM, Culley OJ, Hunter TA, Ma L, Bisceglio GD, Allen M, Dickson DW, Graff-Radford NR, Petersen RC; Genetic and Environmental Risk for Alzheimer’s disease (GERAD1) Consortium, Morgan K, Younkin SG. Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimer's disease pathology. PLoS One. 2013 May 28;8(5):e64802. doi: 10.1371/journal.pone.0064802. Print 2013.

5      Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J; Alzheimer Genetic Analysis Group. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013 Jan 10;368(2):117-27. doi: 10.1056/NEJMoa1211851. Epub 2012 Nov 14.

6      van der Zee J, Gijselinck I, Dillen L, …….., Jessen F, Ramirez A,…….E, Santens P, Cras P; European Early-Onset Dementia Consortium. A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats. Hum Mutat. 2013 Feb;34(2):363-73. doi: 10.1002/humu.22244. Epub 2013 Jan 4.

- Publication 2012

1      Lohmann K, Wilcox RA, Winkler S, Ramirez A, Rakovic A, Park JS, Arns B, Lohnau T, Groen J, Kasten M, Brüggemann N, Hagenah J, Schmidt A, Kaiser FJ, Kumar KR, Zschiedrich K, Alvarez-Fischer D, Altenmüller E, Ferbert A, Lang AE, Münchau A, Kostic V, Simonyan K, Agzarian M, Ozelius LJ, Langeveld AP, Sue CM, Tijssen MA, Klein C. Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. Ann Neurol. 2012 Dec 13. doi: 10.1002/ana.23829. [Epub ahead of print]

2      Dehay B, Martinez-Vicente M, Ramirez A, Perier C, Klein C, Vila M, Bezard E. Lysosomal dysfunction in Parkinson disease: ATP13A2 gets into the groove. Autophagy. 2012 Sep 1;8(9). [Epub ahead of print].

3      Kumar KR, Ramirez A, Göbel A, Kresojević N, Svetel M, Lohmann K, M Sue C, Rolfs A, Mazzulli JR, Alcalay RN, Krainc D, Klein C, Kostic V, Grünewald A. Glucocerebrosidase mutations in a Serbian Parkinson's disease population. Eur J Neurol. 2012 Jul 20. doi: 10.1111/j.1468-1331.2012.03817.x. [Epub ahead of print].

4      Dehay B, Ramirez A, Martinez-Vicente M, Perier C, Canron MH, Doudnikoff E, Vital A, Vila M, Klein C, Bezard E. Loss of P-type ATPase ATP13A2/PARK9 function induces general lysosomal deficiency and leads to Parkinson disease neurodegeneration. Proc Natl Acad Sci U S A. 2012 May 30.

5      Schmitt I, Wüllner U, van Rooyen JP, Khazneh H, Becker J, Volk A, Kubisch C, Becker T, Kostic VS, Klein C, Ramirez A*. Variants in the 3’UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression. Eur J Hum Genet. 2012 Dec;20(12):1265-9. doi: 10.1038/ejhg.2012.84.

6      Grünewald A, Arns B, Seibler P, Rakovic A, Münchau A, Ramirez A, Sue CM, Klein C. ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. Neurobiol Aging. 2012 Aug;33(8):1843.e1-7. doi: 10.1016/j.neurobiolaging.2011.12.035. Epub 2012 Jan 31.

7      Kumar KR, Weissback A, Heldmann M, Kasten M, Tunc S, Sue CM, Svetel M, Kostic VS, Segura-Aguilar J, Ramirez A, Simon DK, Vieregge P, Münte TF, Hagenah J, Klein C, Lohmann K. Frequency of the D620N mutation in VPS35 in Parkinson’s disease. Arch Neurol. 2012 Jul 16:1-5. doi: 10.1001/archneurol.2011.3367.

8      Zittel S, Kroeger J, van der Vegt JP, Siebner HR, Brüggemann N, Ramirez A, Behrens MI, Gerloff C, Bäumer T, Klein C, Münchau A. Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study. Parkinsonism Relat Disord. 2012 Jun;18(5):590-4. doi: 10.1016/j.parkreldis.2011.10.020. Epub 2011 Nov 21.

- Publication 2011

1      Arif B, Grünewald A, Fatima A, Ramirez A, Ali A, Brüggemann N, Würfel J, Rolfs A, Lohmann K, Malik A, Klein C, Naz S. An unusual neurological syndrome of crawling gait, dystonia, pyramidal signs, and limited speech. Mov Disord. 2011 Oct;26(12):2279-83.

2      Ramirez A, Schneider SA, Shafiee K, Kaiser FJ, Erogullari A, Brüggemann N, Winkler S, Bahman I, Osmanovic A, Shafa MA, Bhatia KP, Najmabadi H, Klein C, Lohmann K. Homozygous THAP1 mutations as cause of early-onset generalized dystonia. Mov Disord. 2011 Apr;26(5):858-61.

3      Ramirez A, Ziegler A, Winkler S, Kottwitz A, Giesen R, Díaz-Grez F, Miranda M, Venegas P, Trujillo-Godoy O, Avello R, Behrens MI, Klein C, Segura-Aguilar J, Katja Lohmann K. Association of Parkinson disease to PARK16 in a Chilean cohort. Parkinsonism Relat Disord. 2011 Jan;17(1):70-1.

Our Team

Dr. Markus Leber, PhD
Dr. Amit Kawalia, PhD
Esther Milz, Tech. Assistant

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