(30-07-09) Testing the Neurovascular Hypothesis of Alzheimer's Disease:

LRP-1 Antisense Reduces Blood-brain Barrier Clearance and Increases Brain Levels of Amyloid-beta Protein and Impairs Cognition.


Jaeger LB, Dohgu S, Hwang MC, Farr SA, Murphy MP, Fleegal-Demotta MA, Lynch JL, Robinson SM, Niehoff ML, Johnson SN, Kumar VB, Banks WA.

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri, USA Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, St. Louis, Missouri, USA.
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 Abeta_{42}, increased brain levels of Abeta_{42}, 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.
PMID: 19433890

Source: J Alzheimers Dis. 2009 May 11.

News

---

In evidenza

"L'informazione presente nel sito serve a migliorare, e non a sostituire, il rapporto medico-paziente."

Per coloro che hanno problemi di salute si consiglia di consultare sempre il proprio medico curante.