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The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease.
Curr Pharm Des. 2008; 14(16):1601-5.CP

Abstract

Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer's disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid beta-peptide (Abeta) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Abeta clearance from the brain appears to mediate focal Abeta accumulations in AD. Central and peripheral production of Abeta from Abeta-precursor protein (APP), transport of peripheral Abeta into the brain across the blood-brain barrier (BBB) via receptor for advanced glycation end products (RAGE), enzymatic Abeta degradation, Abeta oligomerization and aggregation, neuroinflammatory changes and microglia activation, and Abeta elimination from brain across the BBB by cell surface LRP; all may control brain Abeta levels. Recently, we have shown that a soluble form of LRP (sLRP) binds 70 to 90 % of plasma Abeta, preventing its access to the brain. In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Abeta binding to sLRP in plasma. This, in turn, may increase Abeta brain levels through a decreased efflux of brain Abeta at the BBB and/or reduced sequestration of plasma Abeta associated with re-entry of free Abeta into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Abeta "sink" activity of sLRP, hold potential to control brain Abeta accumulations, neuroinflammation and cerebral blood flow reductions in AD.

Authors+Show Affiliations

Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. rashid_deane@urmc.rochester.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

18673201

Citation

Deane, R, et al. "The Role of the Cell Surface LRP and Soluble LRP in Blood-brain Barrier Abeta Clearance in Alzheimer's Disease." Current Pharmaceutical Design, vol. 14, no. 16, 2008, pp. 1601-5.
Deane R, Sagare A, Zlokovic BV. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Curr Pharm Des. 2008;14(16):1601-5.
Deane, R., Sagare, A., & Zlokovic, B. V. (2008). The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Current Pharmaceutical Design, 14(16), 1601-5.
Deane R, Sagare A, Zlokovic BV. The Role of the Cell Surface LRP and Soluble LRP in Blood-brain Barrier Abeta Clearance in Alzheimer's Disease. Curr Pharm Des. 2008;14(16):1601-5. PubMed PMID: 18673201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. AU - Deane,R, AU - Sagare,A, AU - Zlokovic,B V, PY - 2008/8/5/pubmed PY - 2008/10/7/medline PY - 2008/8/5/entrez SP - 1601 EP - 5 JF - Current pharmaceutical design JO - Curr. Pharm. Des. VL - 14 IS - 16 N2 - Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer's disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid beta-peptide (Abeta) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Abeta clearance from the brain appears to mediate focal Abeta accumulations in AD. Central and peripheral production of Abeta from Abeta-precursor protein (APP), transport of peripheral Abeta into the brain across the blood-brain barrier (BBB) via receptor for advanced glycation end products (RAGE), enzymatic Abeta degradation, Abeta oligomerization and aggregation, neuroinflammatory changes and microglia activation, and Abeta elimination from brain across the BBB by cell surface LRP; all may control brain Abeta levels. Recently, we have shown that a soluble form of LRP (sLRP) binds 70 to 90 % of plasma Abeta, preventing its access to the brain. In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Abeta binding to sLRP in plasma. This, in turn, may increase Abeta brain levels through a decreased efflux of brain Abeta at the BBB and/or reduced sequestration of plasma Abeta associated with re-entry of free Abeta into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Abeta "sink" activity of sLRP, hold potential to control brain Abeta accumulations, neuroinflammation and cerebral blood flow reductions in AD. SN - 1873-4286 UR - https://www.unboundmedicine.com/medline/citation/18673201/The_role_of_the_cell_surface_LRP_and_soluble_LRP_in_blood_brain_barrier_Abeta_clearance_in_Alzheimer's_disease_ L2 - http://www.eurekaselect.com/67141/article DB - PRIME DP - Unbound Medicine ER -