What we do
About our project
Frontotemporal dementia (FTD) is a clinically heterogeneous neurodegenerative disorder characterized by prominent changes in social behavior and personality or aphasia. In 20-30% of cases, autosomal dominant inheritance is present, most commonly due to mutations in GRN, C9orf72 or MAPT. Biomarkers are needed to aid early diagnosis and to measure effects of disease-modifying therapies, and may lead to a better understanding of the pathophysiology. The presymptomatic stage of genetic FTD provides a unique opportunity to study the earliest changes and develop robust and sensitive biomarkers of disease onset and progression.
What is the aim?
The aim of this study is to identify biomarkers of genetic forms of FTD. These biomarkers are sought in the following modalities:
- Neuroimaging; we investigate genotypic patterns of brain changes using advanced MR imaging and aim to identify sensitive biomarkers predicting conversion from presymptomatic to symptomatic stages.
- Blood or cerebrospinal fluid; we aim to characterize known biomarkers of neurodegeneration (such as neurofilament light chain) as well as identify novel biomarkers.
- Neuropsychological assessment; we study genotypic and phenotypic cognitive profiles in order to find diagnostic and prognostic markers. We validate new cognitive and clinical instruments.
We aim to enlighten the psychological burden of being at-risk for frontotemporal dementia, by developing a Mindfulness based stress reduction program.
How do we perform this research?
Since 2010, we have an ongoing longitudinal cohort study of patients with FTD due to a pathogenic mutation in GRN, MAPT or C9orf72 and their healthy 50% at-risk family members (either presymptomatic mutation carriers or non-carriers). Participants are followed yearly or two-yearly by a neurological and neuropsychological examination, blood sample collection and MR imaging, and in a subset, cerebrospinal fluid collection. Genotyping is performed at the first visit. Clinical investigators are blinded to genetic status of at-risk participants. Data are analyzed for each genotype across three groups: patients with FTD, presymptomatic mutation carriers, and non-carriers (controls).
Funds & Grants
- Deltaplan Dementie (The Netherlands Organisation for Health Research and Development, and Alzheimer Nederland), grant numbers 733050813 and 733050103
- The Bluefield Project to Cure Frontotemporal Dementia
- European Joint Programme – Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042; RiMod-FTD: 733051024)
- Dioraphte Foundation grant 09-02-00
- The Association for frontotemporal Dementias Research Grant 2009
Outside Erasmus MC
Prof. dr. S.A.R.B. Rombouts, department of Radiology, Leiden University Medical Center, Leiden, Netherlands
Prof. dr. C. Teunissen, department of Clinical Chemistry, Amsterdam University Medical Center, Amsterdam, Netherlands
Dr. J.D. Rohrer, Dementia Research Institute, UCL Queen Square Institute of Neurology, London, United Kingdom
- van der Ende et al., 2019. Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal multicentre cohort study. Lancet Neurology.
- Jiskoot et al., 2019. Longitudinal multimodal MRI as prognostic and diagnostic biomarker in presymptomatic familial frontotemporal dementia. Brain.
- Panman et al., 2019. Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study. Neurobiology of Aging.
- Meeter et al., 2018. Clinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum. Neurology.
- Papma et al., 2017. Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology.
- Dopper et al., 2014. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology.
Contact us via email
Emma van der Ende
John van Swieten