Caroline Graff Group

Translational Genetics of Neurodegenerative disease

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 since team members are working both with genetic counselling as well as with research.


Our activities include:

  • studies of families with inherited dementia such as the GENFI study (
  • association studies in case-control cohorts in collaboration with EUEOD, IGAP, EADB, ICFGC,
  • whole genome sequencing in FTD FTLD-TDP WGS Consortium, FTDGSC
  • neuropathological studies of human brain tissue
  • studies of mechanisms of neurodegeneration
  • In vitro studies of patient derived cells such as iPSC
  • single-cell sequencing
  • mechanisms of reduced penetrance
  • functional studies of genetic variation
  • genetic counselling for families with inherited forms of dementia in the Genetics unit, Theme Aging, Karolinska University Hospital, Solna
  • screening patient samples from the clinic for mutations in known disease causing genes and apply our result in a clinical genetics setting

Research projects

Below follows a description of two of our research projects:

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 been temporarily shut-down July-December 2018. But as of 2019 the Brain Bank has been granted infrastructure funding from CIMED (2019-2021) and therefore its core facility services will be re-activated. Please see the webpage for more information (
The continued goal is to manage human brain and spinal cord tissue for research.
The Brain Bank has a brain donation program for informed consent and standardized collection of high quality nervous tissue.

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 future clinical trials in this group of patients with early onset autosomal dominant disease.  Naturally being brought up in families with inherited forms of neurodegenerative disease has an effect on the family members on an existential and emotional level. Thus, we conduct quantitative (questionnaires) and qualitative (interviews) studies to get a better understanding of what it is like to live with the risk to develop early onset AD.

We are partners in several national and international collaborations such as: GENFI (Genetic FTD initiative), Swedish Brain Power, Strat Neuro, Brain Net Europe, IGAP (International Genomics of Alzheimer’s Project), ECEOD (European Consortium on Early Onset Dementia, EADC (European Alzheimer Disease Consortium) and FTD-GWAS. 

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 characterzed by behavioural changes and or language dysfunction. 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. We are partners of the international Genetic FTD intitiative ( and we have recently initiated a National consortia called Swedish FTD Inititative.

Research group leader

Caroline Graff

Professor/specialist physician

Group members

Abbe Ullgren

PhD student

Behzad Khoshnood

Postdoctoral researcher

Emma Ehn

PhD Student

Jessica Pege

Research coordinator

Jose Laffita

Laboratory manager

Kalicharan Patra

Laboratory coordinator

Marléne Rosvall

Affiliated to research

Nathalie Asperen

Affiliated to research

Selected publications

Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease.
Almkvist O, Rodriguez-Vieitez E, Thordardottir S, Amberla K, Axelman K, Basun H, et al
J Int Neuropsychol Soc 2017 03;23(3):195-203

TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
van der Zee J, Gijselinck I, Van Mossevelde S, Perrone F, Dillen L, Heeman B, et al
Hum. Mutat. 2017 03;38(3):297-309

Defeating Alzheimer's disease and other dementias: a priority for European science and society.
Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, et al
Lancet Neurol 2016 Apr;15(5):455-532

Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy.
Piras A, Collin L, Grüninger F, Graff C, Rönnbäck A
Acta Neuropathol Commun 2016 Mar;4():22

Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease.
Rodriguez-Vieitez E, Saint-Aubert L, Carter S, Almkvist O, Farid K, Schöll M, et al
Brain 2016 Mar;139(Pt 3):922-36

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis.
Rohrer J, Nicholas J, Cash D, van Swieten J, Dopper E, Jiskoot L, et al
Lancet Neurol 2015 Mar;14(3):253-62

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis.
Rohrer J, Nicholas J, Cash D, van Swieten J, Dopper E, Jiskoot L, et al
Lancet Neurol 2015 Mar;14(3):253-62

Preclinical cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers in Swedish familial Alzheimer's disease.
Thordardottir S, Ståhlbom A, Ferreira D, Almkvist O, Westman E, Zetterberg H, et al
J. Alzheimers Dis. 2015 ;43(4):1393-402

Frontotemporal dementia and its subtypes: a genome-wide association study.
Ferrari R, Hernandez D, Nalls M, Rohrer J, Ramasamy A, Kwok J, et al
Lancet Neurol 2014 Jul;13(7):686-99

Neuropathological characterization of two siblings carrying the MAPT S305S mutation demonstrates features resembling argyrophilic grain disease.
Rönnbäck A, Nennesmo I, Tuominen H, Grueninger F, Viitanen M, Graff C
Acta Neuropathol. 2014 Feb;127(2):297-8

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration.
Chiang H, Forsell C, Lilius L, Öijerstedt L, Thordardottir S, Shanmugarajan K, et al
Eur. J. Hum. Genet. 2013 Nov;21(11):1260-5