Translational Genetics of Neurodegenerative disease – Caroline Graff's research group

Research focus

We study the genetics and neuropathology of neurodegenerative diseases in particular Alzheimer disease (AD), Frontotemporal lobar degeneration (FTLD) and FTLD associated with amyotrophic lateral sclerosis (ALS). Our research is translational from patients and families to the laboratory and back. If you are interested to participate in research please contact us via NVS Kliniskforskning Graff (kliniskforskning-graff@nvs.ki.se) or contact one of the group members directly.

Activities

Our activities include:

  • Clinical follow-up studies of families with inherited neurodegenerative diseases to describe the pathological staging of disease in particular
    • the GENFI study (genfi.org) and
    • a study on dominantly inherited Alzheimer disease
  • Recruit clinical treatment trials for genetic forms of FTD within the framework of (thefpi.org)
  • Whole genome sequencing to identify known and unknown genetic factors in early onset cognitive diseases
  • We host a webpage for and organize the activites in the Swedish FTD Initiative (frontallobsdemens.se)
  • We participate in global association studies in case-control cohorts in AD and
  • Neuropathological studies of human brain tissue
  • We imnplement our research in close collaboration with the out-patient clinic at the Unit for hereditary dementia, (Mottagning för ärftliga demenssjukdomar) Clinical Genetics, Karolinska University Hospital, Solna.
  • We have large sample collections of DNA, fibroblasts, RNA, plasma, serum and CSF.
  • FTD such as IGAP (International Genomics of Alzheimer’s Project), ECEOD (European Consortium on Early Onset Dementia, EADC (European Alzheimer Disease Consortium) and FTD-GWAS, ICFGC and whole genome sequencing projects such as the FTLD-TDP WGS Consortium, FTDGSC

Research projects

Below follows a description of two of our research projects:

Experimental and clinical studies of inherited forms of dementia

Of particular interest is to develop biomarkers for early diagnosis in AD and FTLD which we do by studying family members with 50% risk of inheriting a dominant disease causing mutation. During the course of the study the study subjects perform an extensive battery of clinical examinations as well as tissue sampling. Our hope is to better understand the natural history of AD and FTLD respectively, develop specific and sensitive biomarkers for early diagnosis and identify new drug targets. We also hope that our research will facilitate recruiting clinical trials for this group of families with early onset autosomal dominant disease. Currently we have two ongoing clinical trials in collaboration with the Clinical Trials Unit, Karolinska University Hospital Huddinge, for progranulin and C9orf72 mutation carriers diagnosed with FTD or ALS.

Our studies on genetic FTD are part of a European Canadian  FTD studies We are partners of the international Genetic FTD intitiative (genfi.org) and we lead a national network on FTD called Swedish FTD Initiative. SweFTDI is engaged in experimental and clinical research and organize all interest groups in FTD i.e. clinicians, researchers, care givers, patients and families. On our webpage you can find  current activities and publications such as “Clinical guidelines for FTD” available via the website (Frontallobsdemens.se).

Frontotemporal dementia (FTD)

FTD is a group of neurodegenerative diseases characterized by neuronal dysfunction in the anterior temporal lobes and frontal lobes. The clinical symptoms are characterized by behavioural changes and or language dysfunctions. There is a clinical, genetic and neuropathological overlap with ALS (amyotrophic lateral sclerosis). We investigate the genetics and neuropathology of FTD in both clinical studies of at-risk subjects as well as experimental studies of patient derived cells and fluids. Please visit our homepage at Swedish FTD Inititative (frontallobsdemens.se) for more information about FTD, details on diagnostic criteria and ongoing activities.

The Brain Bank at Karolinska Institutet

The Brain Bank at Karolinska Institutet was a core-facility between 2013-2018. Due to a temporary termination of funding the activities and webpage was temporarily shut-down July-December 2018. Again in 2019 the Brain Bank was granted infrastructure funding from CIMED (2019-2021). However, as of 2022 we have limited services but are happy to provide access to available tissue if possible, upon request.  Please see the webpage for more information (http://www.ki.se/brainbank).
The continued goal is to manage human brain and spinal cord tissue for research.
We are currently discussing possible solutions for future biobanking in collaboration with the Karolinska University Hospital.

Publications

Selected publications

  • Review: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. 2021;92(2):204-215
    Swift IJ; Sogorb-Esteve A; Heller C; Synofzik M; Otto M; Graff C; Galimberti D; Todd E; Heslegrave AJ; van der Ende EL; Van Swieten JC; Zetterberg H; Rohrer JD
  • Article: JOURNAL OF ALZHEIMER'S DISEASE. 2020;76(3):941-953
    Thordardottir S; Almkvist O; Johansson C; Zetterberg H; Blennow K; Graff C
  • Article: TRANSLATIONAL NEURODEGENERATION. 2020;9(1):27
    Remnestal J; Oijerstedt L; Ullgren A; Olofsson J; Bergstrom S; Kultima K; Ingelsson M; Kilander L; Uhlen M; Manberg A; Graff C; Nilsson P
  • Article: LANCET NEUROLOGY. 2020;19(2):145-156
    Moore KM; Nicholas J; Grossman M; McMillan CT; Irwin DJ; Massimo L; Van Deerlin VM; Warren JD; Fox NC; Rossor MN; Mead S; Bocchetta M; Boeve BF; Knopman DS; Graff-Radford NR; Forsberg LK; Rademakers R; Wszolek ZK; van Swieten JC; Jiskoot LC; Meeter LH; Dopper EGP; Papma JM; Snowden JS; Saxon J; Jones M; Pickering-Brown S; Le Ber I; Camuzat A; Brice A; Caroppo P; Ghidoni R; Pievani M; Benussi L; Binetti G; Dickerson BC; Lucente D; Krivensky S; Graff C; Oijerstedt L; Fallstrom M; Thonberg H; Ghoshal N; Morris JC; Borroni B; Benussi A; Padovani A; Galimberti D; Scarpini E; Fumagalli GG; Mackenzie IR; Hsiung G-YR; Sengdy P; Boxer AL; Rosen H; Taylor JB; Synofzik M; Wilke C; Sulzer P; Hodges JR; Halliday G; Kwok J; Sanchez-Valle R; Llado A; Borrego-Ecija S; Santana I; Almeida MR; Tabuas-Pereira M; Moreno F; Barandiaran M; Indakoetxea B; Levin J; Danek A; Rowe JB; Cope TE; Otto M; Anderl-Straub S; de Mendonca A; Maruta C; Masellis M; Black SE; Couratier P; Lautrette G; Huey ED; Sorbi S; Nacmias B; Laforce RJ; Tremblay M-PL; Vandenberghe R; Van Damme P; Rogalski EJ; Weintraub S; Gerhard A; Onyike CU; Ducharme S; Papageorgiou SG; Ng ASL; Brodtmann A; Finger E; Guerreiro R; Bras J; Rohrer JD; Heller C; Convery R; Woollacott IOC; Shafei R; Graff-Radford J; Jones DT; Dheel CM; Savica R; Lapid MI; Baker M; Fields JA; Gavrilova R; Domoto-Reilly K; Poos JM; van der Ende EL; Panman JL; Kaat LD; Seelaar H; Richardson A; Frisoni G; Mega A; Fostinelli S; Chiang H-H; Alberici A; Arighi A; Fenoglio C; Heuer H; Miller B; Karydas A; Fong J; Leitao MJ; Santiago B; Duro D; Ferreira C; Gabilondo A; de Arriba M; Tainta M; Zulaica M; Ferreira CB; Semler E; Ludolph A; Landwehrmeyer B; Volk AE; Miltenberger G; Verdelho A; Afonso S; Tartaglia MC; Freedman M; Rogaeva E; Ferrari C; Piaceri I; Bessi V; Lombardi G; St-Onge F; Dore M-C; Bruffaerts R; Vandenbulcke M; Van den Stock J; Mesulam MM; Bigio E; Koros C; Papatriantafyllou J; Kroupis C; Stefanis L; Shoesmith C; Roberson E; Coppola G; Ramos EMDS; Geschwind D
  • Article: NEUROBIOLOGY OF AGING. 2019;84:241.e21-241.e25
    Oijerstedt L; Chiang H-H; Bjorkstrom J; Forsell C; Lilius L; Lindstrom A-K; Thonberg H; Graff C
  • Article: JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY. 2017;23(3):195-203
    Almkvist O; Rodriguez-Vieitez E; Thordardottir S; Amberla K; Axelman K; Basun H; Kinhult-Stahlbom A; Lilius L; Remes A; Wahlund L-O; Viitanen M; Lannfelt L; Graff C
  • Article: HUMAN MUTATION. 2017;38(3):297-309
    van der Zee J; Gijselinck I; Van Mossevelde S; Perrone F; Dillen L; Heeman B; Baumer V; Engelborghs S; De Bleecker J; Baets J; Gelpi E; Rojas-Garcia R; Clarimon J; Lleo A; Diehl-Schmid J; Alexopoulos P; Perneczky R; Synofzik M; Just J; Schoels L; Graff C; Thonberg H; Borroni B; Padovani A; Jordanova A; Sarafov S; Tournev I; de Mendonca A; Miltenberger-Miltenyi G; Simoes do Couto F; Ramirez A; Jessen F; Heneka MT; Gomez-Tortosa E; Danek A; Cras P; Vandenberghe R; De Jonghe P; De Deyn PP; Sleegers K; Cruts M; Van Broeckhoven C
  • Article: LANCET NEUROLOGY. 2016;15(5):455-532
    Winblad B; Amouyel P; Andrieu S; Ballard C; Brayne C; Brodaty H; Cedazo-Minguez A; Dubois B; Edvardsson D; Feldman H; Fratiglioni L; Frisoni GB; Gauthier S; Georges J; Graff C; Iqbal K; Jessen F; Johansson G; Jonsson L; Kivipelto M; Knapp M; Mangialasche F; Melis R; Nordberg A; Rikkert MO; Qiu C; Sakmar TP; Scheltens P; Schneider LS; Sperling R; Tjernberg LO; Waldemar G; Wimo A; Zetterberg H
  • Article: BRAIN. 2016;139(Pt 3):922-936
    Rodriguez-Vieitez E; Saint-Aubert L; Carter SF; Almkvist O; Farid K; Scholl M; Chiotis K; Thordardottir S; Graff C; Wall A; Langstrom B; Nordberg A
  • Article: LANCET NEUROLOGY. 2015;14(3):253-262
    Rohrer JD; Nicholas JM; Cash DM; van Swieten J; Dopper E; Jiskoot L; van Minkelen R; Rombouts SA; Cardoso MJ; Clegg S; Espak M; Mead S; Thomas DL; De Vita E; Masellis M; Black SE; Freedman M; Keren R; MacIntosh BJ; Rogaeva E; Tang-Wai D; Tartaglia MC; Laforce RJ; Tagliavini F; Tiraboschi P; Redaelli V; Prioni S; Grisoli M; Borroni B; Padovani A; Galimberti D; Scarpini E; Arighi A; Fumagalli G; Rowe JB; Coyle-Gilchrist I; Graff C; Fallstrom M; Jelic V; Stahlbom AK; Andersson C; Thonberg H; Lilius L; Frisoni GB; Pievani M; Bocchetta M; Benussi L; Ghidoni R; Finger E; Sorbi S; Nacmias B; Lombardi G; Polito C; Warren JD; Ourselin S; Fox NC; Rossor MN
  • Article: JOURNAL OF ALZHEIMER'S DISEASE. 2014;43(4):1393-1402
    Thordardottir S; Stahlbom AK; Ferreira D; Almkvist O; Westman E; Zetterberg H; Eriksdotter M; Blennow K; Graff C
  • Article: LANCET NEUROLOGY. 2014;13(7):686-699
    Ferrari R; Hernandez DG; Nalls MA; Rohrer JD; Ramasamy A; Kwok JBJ; Dobson-Stone C; Brooks WS; Schofield PR; Halliday GM; Hodges JR; Piguet O; Bartley L; Thompson E; Haan E; Hernandez I; Ruiz A; Boada M; Borroni B; Padovani A; Cruchaga C; Cairns NJ; Benussi L; Binetti G; Ghidoni R; Forloni G; Galimberti D; Fenoglio C; Serpente M; Scarpini E; Clarimon J; Lleo A; Blesa R; Waldo ML; Nilsson K; Nilsson C; Mackenzie IRA; Hsiung G-YR; Mann DMA; Grafman J; Morris CM; Attems J; Griffiths TD; McKeith IG; Thomas AJ; Pietrini P; Huey ED; Wassermann EM; Baborie A; Jaros E; Tierney MC; Pastor P; Razquin C; Ortega-Cubero S; Alonso E; Perneczky R; Diehl-Schmid J; Alexopoulos P; Kurz A; Rainero I; Rubino E; Pinessi L; Rogaeva E; St George-Hyslop P; Rossi G; Tagliavini F; Giaccone G; Rowe JB; Schlachetzki JCM; Uphill J; Collinge J; Mead S; Danek A; Van Deerlin VM; Grossman M; Trojanowski JQ; van der Zee J; Deschamps W; Van Langenhove T; Cruts M; Van Broeckhoven C; Cappa SF; Le Ber I; Hannequin D; Golfier V; Vercelletto M; Brice A; Nacmias B; Sorbi S; Bagnoli S; Piaceri I; Nielsen JE; Hjermind LE; Riemenschneider M; Mayhaus M; Ibach B; Gasparoni G; Pichler S; Gu W; Rossor MN; Fox NC; Warren JD; Spillantini MG; Morris HR; Rizzu P; Heutink P; Snowden JS; Rollinson S; Richardson A; Gerhard A; Bruni AC; Maletta R; Frangipane F; Cupidi C; Bernardi L; Anfossi M; Gallo M; Conidi ME; Smirne N; Rademakers R; Baker M; Dickson DW; Graff-Radford NR; Petersen RC; Knopman D; Josephs KA; Boeve BF; Parisi JE; Seeley WW; Miller BL; Karydas AM; Rosen H; van Swieten JC; Dopper EGP; Seelaar H; Al Pijnenburg Y; Scheltens P; Logroscino G; Capozzo R; Novelli V; Puca AA; Franceschi M; Postiglione A; Milan G; Sorrentino P; Kristiansen M; Chiang H-H; Graff C; Pasquier F; Rollin A; Deramecourt V; Lebert F; Kapogiannis D; Ferrucci L; Pickering-Brown S; Singleton AB; Hardy J; Momeni P

Staff and contact

Group leader

All members of the group