Tags

Type your tag names separated by a space and hit enter

Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition.
J Alzheimers Dis. 2009; 17(3):553-70.JA

Abstract

Decreased clearance is the main reason amyloid-beta protein (Abeta) is increased in the brains of patients with Alzheimer's disease (AD). The neurovascular hypothesis states that this decreased clearance is caused by impairment of low density lipoprotein receptor related protein-1 (LRP-1), the major brain-to-blood transporter of Abeta at the blood-brain barrier (BBB). As deletion of the LRP-1 gene is a lethal mutation, we tested the neurovascular hypothesis by developing a cocktail of phosphorothioate antisenses directed against LRP-1 mRNA. We found these antisenses in comparison to random antisense selectively decreased LRP-1 expression, reduced BBB clearance of Abeta42, increased brain levels of Abeta42, and impaired learning ability and recognition memory in mice. These results support dysfunction of LRP-1 at the BBB as a mechanism by which brain levels of Abeta could increase and AD would be promoted.

Authors+Show Affiliations

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19433890

Citation

Jaeger, Laura B., et al. "Testing the Neurovascular Hypothesis of Alzheimer's Disease: LRP-1 Antisense Reduces Blood-brain Barrier Clearance, Increases Brain Levels of Amyloid-beta Protein, and Impairs Cognition." Journal of Alzheimer's Disease : JAD, vol. 17, no. 3, 2009, pp. 553-70.
Jaeger LB, Dohgu S, Hwang MC, et al. Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition. J Alzheimers Dis. 2009;17(3):553-70.
Jaeger, L. B., Dohgu, S., Hwang, M. C., Farr, S. A., Murphy, M. P., Fleegal-DeMotta, M. A., Lynch, J. L., Robinson, S. M., Niehoff, M. L., Johnson, S. N., Kumar, V. B., & Banks, W. A. (2009). Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition. Journal of Alzheimer's Disease : JAD, 17(3), 553-70. https://doi.org/10.3233/JAD-2009-1074
Jaeger LB, et al. Testing the Neurovascular Hypothesis of Alzheimer's Disease: LRP-1 Antisense Reduces Blood-brain Barrier Clearance, Increases Brain Levels of Amyloid-beta Protein, and Impairs Cognition. J Alzheimers Dis. 2009;17(3):553-70. PubMed PMID: 19433890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition. AU - Jaeger,Laura B, AU - Dohgu,Shinya, AU - Hwang,Mark C, AU - Farr,Susan A, AU - Murphy,M Paul, AU - Fleegal-DeMotta,Melissa A, AU - Lynch,Jessica L, AU - Robinson,Sandra M, AU - Niehoff,Michael L, AU - Johnson,Steven N, AU - Kumar,Vijaya B, AU - Banks,William A, PY - 2009/5/13/entrez PY - 2009/5/13/pubmed PY - 2009/12/16/medline SP - 553 EP - 70 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 17 IS - 3 N2 - Decreased clearance is the main reason amyloid-beta protein (Abeta) is increased in the brains of patients with Alzheimer's disease (AD). The neurovascular hypothesis states that this decreased clearance is caused by impairment of low density lipoprotein receptor related protein-1 (LRP-1), the major brain-to-blood transporter of Abeta at the blood-brain barrier (BBB). As deletion of the LRP-1 gene is a lethal mutation, we tested the neurovascular hypothesis by developing a cocktail of phosphorothioate antisenses directed against LRP-1 mRNA. We found these antisenses in comparison to random antisense selectively decreased LRP-1 expression, reduced BBB clearance of Abeta42, increased brain levels of Abeta42, and impaired learning ability and recognition memory in mice. These results support dysfunction of LRP-1 at the BBB as a mechanism by which brain levels of Abeta could increase and AD would be promoted. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/19433890/Testing_the_neurovascular_hypothesis_of_Alzheimer's_disease:_LRP_1_antisense_reduces_blood_brain_barrier_clearance_increases_brain_levels_of_amyloid_beta_protein_and_impairs_cognition_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=17&issue=3&spage=553 DB - PRIME DP - Unbound Medicine ER -