Name of Fellow

    Dr. M.A. van Es




    Contact information of fellow


    The Netherlands

    Title of project/programme

    Genetic pleiotropy in neurodegeneration

    Source of funding information


    Total sum awarded (Euro)

    € 250,000

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Alzheimer's disease & other dementias


    Genetics | Neurodegeneration | Alzheimer’s | FTD | ALS

    Research Abstract

    Alzheimer’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS are severely disabling and fatal
    neurodegenerative diseases. Although they have very characteristic phenotypes (Alzheimer’s disease: progressive memory
    loss, ALS: progressive weakness), there are also many commonalities. They are late onset, progressive diseases in which
    there is aggregation of specific proteins. The etiology of most neurodegenerative diseases remains poorly understood, but
    there is mounting evidence that genetic risk factors play a large role.
    Interestingly patients affected by neurodegenerative disorders may also develop (features of) other neurodegenerative
    diseases. For instance FTD patients may develop ALS, ALS patients can show signs of parkinsonism, etc. Recently several
    genes have been identified that seem to cause multiple neurodegenerative disorders of which C9orf72 is perhaps the most
    spectacular and has been implicated in FTD, ALS, parkinsonism, ataxia and psychosis. Other examples of pleiotropic genes
    are ANG, FUS, MAPT and TARDBP. Most neurodegenerative disorders can present as familial or sporadic disease. Even
    within families, where the disease is assumed to be due to a single mutation, there is high phenotypic variability and
    non-penetrance is frequently observed. The main hypothesis underlying this proposal is that there are genes that predispose to
    neurodegeneration in general and that it is the sum of mutations across multiple genes that determine phenotype. Recently
    there have been several publications describing patients with mutations in multiple neurodegenerative genes. I propose that
    phenotypic variability, overlap between disorders and non-penetrance are due to oligogenic inheritance of pleiotropic genes.
    This hypothesis will be tested by analyzing whole exome sequencing data from large cohorts of Alzheimer’s, FTD, ALS patients
    and controls. We will search for multiple risk factors within diseases as well as across different disorders

Types: Fellowships
Member States: Netherlands
Diseases: Alzheimer's disease & other dementias
Years: 2016
Database Categories: N/A
Database Tags: N/A

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