Principal Investigators

    Jens Pahnke

    Institution

    University of Oslo

    Contact information of lead PI

    Country

    Norway

    Title of project or programme

    The role of the blood-brain barrier in Alzheimers disease function

    Source of funding information

    RCN

    Total sum awarded (Euro)

    € 749,220

    Start date of award

    01/01/2016

    Total duration of award in years

    3.0

    The project/programme is most relevant to:

    Alzheimer's disease & other dementias

    Keywords

    Research Abstract

    The blood-brain barrier is increasingly moving into the focus of neurodegeneration research for the homeostasis of toxic peptides in the brain. In Alzheimer’s disease, the aggregation of amyloid-beta peptides (Abeta) represents one of the classical histological hallmarks. It is still debated whether Aß is the pathogenic agent itself or just a marker for the cognitive decline in elderly patients. To date, vascular Abeta has been regarded as an important marker for the distraction of the brains nutrition and its protecting barrier. Active export of beta by receptors and transcytotic mechanisms as well as channel proteins that facilitate active transport have been described recently by us and others. Specifically, LRP1 and ABC transporters may interact and regulate the blood-brain barrier (BBB) export and import function. The proposed project will investigate the functional network and interactions of the three key Abeta-transporters: LRP1, ABCB1, and ABCC1. We hypothesize that lipoprotein receptors and ABC transporters operate together in a tightly regulated fashion to transport Aß peptides out of the brain parenchyma and that alterations in this balance will accelerate AD development. We will use newly developed single and double-knockout mice which will enable us to identify the interplay of LRP1 with different ABC transporters at the endothelial cell layer of the BBB. The interaction and regulation of Aß in the setting of LRP1-deficiency together with the two ABC transporters will enable us to highlight for the first time the interaction of both mechanisms that so far have only been regarded separately.

    Lay Summary

    Further information available at:

Types: Investments > €500k
Member States: Norway
Diseases: Alzheimer's disease & other dementias
Years: 2016
Database Categories: N/A
Database Tags: N/A

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