Low-Density Lipoprotein Receptor-Related Protein 2 Clears Amyloid-Beta Peptide A cross the Blood-Brain Barrier via Apolipoprotein J
OwnerBerislav V. Zlokovic, Rashid Deaneinventors
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Abstract
Low-density lipoprotein receptor-related protein 2 (LRP2) is a potential receptor to regulate the level of apolipoprotein J (apoJ) in the central nervous system, which is the major carrier of amyloid-β peptide (Aβ). ApoJ is cleared from brain interstitial fluid (ISF) and cerebrospinal fluid (CSF) by LRP2-mediated transcytosis across epithelial and endothelial barriers. At physiological ISF/CSF levels, apoJ is rapidly transported by LRP2 across the blood-brain barrier (BBB). Importantly, apoJ also substantially enhances clearance from the brain of amyloidogenic Aβ isoforms (i.e., higher β-sheet content such as Aβ42) as apoJ-Aβ by LRP2-mediated transport.
Claims11
A method of at least diagnosing a subject with Alzheimer's disease or identifying a subject as being at risk for developing Alzheimer's disease, said method comprising:
- (a) measuring at least abundance of low-density lipoprotein receptor-related protein 2 (LRP2), abundance of transcripts thereof, or LRP2 receptor activity in a subject;
- (b) comparing the abundance of LRP2 protein, abundance of transcripts thereof, or activity of LRP2 receptor in the subject to at least an age-matched control not affected by Alzheimer's disease;
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- (c) at least diagnosing the subject with Alzheimer's disease or identifying the subject as being at risk for developing Alzheimer's disease when the abundance of LRP2 protein, abundance of transcripts thereof, or activity of LRP2 receptor in the subject is decreased relative to said age-matched control not affected by Alzheimer's disease.
A method of at least treating a subject with Alzheimer's disease or at risk for developing Alzheimer's disease, said method comprising increasing low-density lipoprotein receptor-related protein 2 (LRP2)-mediated removal of amyloid-β peptide (Aβ) at the blood-brain barrier in the subject in the direction from brain to blood or increasing low-density lipoprotein receptor-related protein 2 (LRP2)-mediated clearance of amyloid-β peptide (Aβ) from the central nervous system of the subject.
A method of determining the effectiveness of at least a drug or medical regimen for treating Alzheimer's disease, said method comprising:
- (a) measuring the abundance of low-density lipoprotein receptor-related protein 2 (LRP2), abundance of transcripts thereof, or activity of LRP2 receptor in the presence of said drug or medical regimen, and
- (b) at least determining said drug or medical regimen is effective when the abundance of LRP2 protein, abundance of transcripts thereof, or activity of LRP2 receptor is increased in the presence of said drug or medical regimen.
Dependencies are inferred from the claim text.