Principal Investigators




    Contact information of lead PI



    Title of project or programme

    Understanding the role of MAPT in Parkinsonian disorders

    Source of funding information


    Total sum awarded (Euro)

    € 1,541,337.61

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    Progressive Supranuclear Palsy, Parkinsonian Disorders, Parkinson Disease, MAPT gene, rare variant

    Research Abstract

    DESCRIPTION (provided by applicant): Mutations within the MAPT gene encoding the microtubule-associated protein tau result in the clinical phenotype of frontotemporal dementia with parkinsonism or progressive supranuclear palsy (PSP) both displaying predominant tau pathology at autopsy. Common variants at the MAPT locus further define two non- recombining MAPT haplotypes (MAPT H1 and H2) resulting from an ancient inversion. Recent genome-wide association studies have implicated MAPT H1 as a significant risk factor for both Parkinson’s disease (PD) and PSP; however preliminary sub-haplotype analyses suggest that different genetic variants on the MAPT H1 haplotype associate with each of these parkinsonian disorders. It currently remains unclear which variation at the MAPT locus is responsible for the risk and what is the underlying pathomechanism of disease. This project sets out to resolve the disease-associated genetic variation within the MAPT locus for both PD and PSP patients, to characterize the prevalence and effect size and to determine the functional consequence. The Specific Aims are focused on 1) identification of genetic variants in the MAPT genomic region through next-generation sequencing of 350 PD, 350 PSP and 350 controls using a DNA pooling strategy; 2) genetic association analyses of common and rare variants in MAPT in extensive PD and PSP case-control populations; and 3) study of the effect of MAPT variants on MAPT transcription, translation and alternative splicing in vitro and in human brain. The proposed studies are relevant to fully appreciate the contribution of common and rare variants in MAPT to the development of parkinsonian disorders and will contribute to a better understanding of the disease mechanism associated with tau dysfunction in PD and PSP.

    Lay Summary

    PROJECT NARRATIVE This proposal is designed to determine the full contribution of common and rare variants in MAPT to the development of the two most common parkinsonian disorders, PD and PSP. The proposed studies will contribute to our understanding of and our ability to treat patients with parkinsonism through improved patient diagnosis, the ability to develop novel etiologic disease models and an increased understanding of the MAPT associated pathomechanism(s), which may ultimately inform possible therapeutic strategies.

    Further information available at:

Types: Investments > €500k
Member States: United States of America
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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