Role of LRP1 in production and degradation of ABeta

Anton Roebroek, PhD
Katholieke Universiteit Leuven (Leuven, Belgium)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2010
Disease:
Alzheimer's Disease
Award Amount:
$240,000
Grant Reference ID:
A2007096
Award Type:
Standard
Award Region:
International
Anton Roebroek, PhD

The Dual Role of LRP1 in Generation and Clearance of Ab

Summary

Recent scientific investigations revealed that a receptor, LRP1, present on the outside of the cells in the brain might be involved at the same time in both production and breakdown of Ab. Lately, the applicant of the research project generated mice and cells with a modified LRP1, which can be used to clarify the double role of LRP1 in Ab metabolism.

Details


Alzheimer's Disease (AD) is caused by the increasing appearance of abnormal structures in the brain of AD patients, named senile plaques. These plaques consist mainly out of aggregates of a small peptide, Ab, which arises from cleavage from a larger protein. Ab is also present in the brain of healthy people, but for some reason the amount of Ab in the brain goes strongly up and it is deposited in the senile plaques in AD patients. It seems that the normal balance between production and breakdown of Ab, in scientific terms Ab metabolism, is disturbed. Recent scientific investigations revealed that a receptor, LRP1, present on the outside of the cells in the brain might be involved at the same time in both production and breakdown of Ab. Lately, the applicant of the research project generated mice and cells with a modified LRP1, which can be used to clarify the double role of LRP1 in Ab metabolism. It is the strong belief of the applicant that this scientific research will result in essential additional knowledge on the role of LRP1 in the balance of production and breakdown of Ab. This could eventually contribute to new approaches for a treatment for AD.

Publications

Pflanzner, T., Janko, M.C., Andre-Dohmen B., Reuss, S., Weggen, S., Roebroek, A., Kuhlmann, C.R.W. and Pietrzik, C.U. LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brainbarrier. Neurobiol Aging. 2010 Jul 12.  

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