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Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease.
Mech Ageing Dev. 2008 Nov; 129(11):649-55.MA

Abstract

Accumulation of beta-amyloid (Abeta) peptide in the brain is a major hallmark of Alzheimer's disease (AD). Hypercholesterolemia is a risk factor for AD and has been shown by laboratory studies to cause Abeta accumulation. Abeta levels in the brain are governed by its generation from amyloid precursor protein by beta-secretase (BACE1), degradation by the insulin degrading enzyme (IDE), clearance from the brain by the low density lipoprotein receptor-related protein (LRP-1), and transport from circulation into the brain by receptor for advanced glycation end products (RAGE). However, the mechanisms by which hypercholesterolemia causes Abeta accumulation in the brain and contributes to the pathogenesis of AD are still to be determined. In the present study, we determined the extent to which hypercholesterolemia-induced Abeta accumulation is associated with alterations in BACE1, IDE, LRP-1, and RAGE expression levels. We show that hypercholesterolemia increases Abeta production, an effect that is associated with increased levels of BACE1 and RAGE and reduced levels of IDE and LRP-1. These results suggest that reducing Abeta accumulation in the brain may require strategies that combine reduction of generation and transport of Abeta in addition to acceleration of degradation and clearance of this peptide.

Authors+Show Affiliations

Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58202, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18845178

Citation

Jaya Prasanthi, R P., et al. "Regulation of Beta-amyloid Levels in the Brain of Cholesterol-fed Rabbit, a Model System for Sporadic Alzheimer's Disease." Mechanisms of Ageing and Development, vol. 129, no. 11, 2008, pp. 649-55.
Jaya Prasanthi RP, Schommer E, Thomasson S, et al. Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. Mech Ageing Dev. 2008;129(11):649-55.
Jaya Prasanthi, R. P., Schommer, E., Thomasson, S., Thompson, A., Feist, G., & Ghribi, O. (2008). Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. Mechanisms of Ageing and Development, 129(11), 649-55. https://doi.org/10.1016/j.mad.2008.09.002
Jaya Prasanthi RP, et al. Regulation of Beta-amyloid Levels in the Brain of Cholesterol-fed Rabbit, a Model System for Sporadic Alzheimer's Disease. Mech Ageing Dev. 2008;129(11):649-55. PubMed PMID: 18845178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. AU - Jaya Prasanthi,R P, AU - Schommer,Eric, AU - Thomasson,Sarah, AU - Thompson,Alex, AU - Feist,Gwen, AU - Ghribi,Othman, Y1 - 2008/09/19/ PY - 2008/05/27/received PY - 2008/08/12/revised PY - 2008/09/08/accepted PY - 2008/10/11/pubmed PY - 2009/3/6/medline PY - 2008/10/11/entrez SP - 649 EP - 55 JF - Mechanisms of ageing and development JO - Mech. Ageing Dev. VL - 129 IS - 11 N2 - Accumulation of beta-amyloid (Abeta) peptide in the brain is a major hallmark of Alzheimer's disease (AD). Hypercholesterolemia is a risk factor for AD and has been shown by laboratory studies to cause Abeta accumulation. Abeta levels in the brain are governed by its generation from amyloid precursor protein by beta-secretase (BACE1), degradation by the insulin degrading enzyme (IDE), clearance from the brain by the low density lipoprotein receptor-related protein (LRP-1), and transport from circulation into the brain by receptor for advanced glycation end products (RAGE). However, the mechanisms by which hypercholesterolemia causes Abeta accumulation in the brain and contributes to the pathogenesis of AD are still to be determined. In the present study, we determined the extent to which hypercholesterolemia-induced Abeta accumulation is associated with alterations in BACE1, IDE, LRP-1, and RAGE expression levels. We show that hypercholesterolemia increases Abeta production, an effect that is associated with increased levels of BACE1 and RAGE and reduced levels of IDE and LRP-1. These results suggest that reducing Abeta accumulation in the brain may require strategies that combine reduction of generation and transport of Abeta in addition to acceleration of degradation and clearance of this peptide. SN - 0047-6374 UR - https://www.unboundmedicine.com/medline/citation/18845178/Regulation_of_beta_amyloid_levels_in_the_brain_of_cholesterol_fed_rabbit_a_model_system_for_sporadic_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0047-6374(08)00174-7 DB - PRIME DP - Unbound Medicine ER -