LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-β peptide in a blood-brain barrier in vitro model

Babak Nazer, Soyon Hong, Dennis J. Selkoe

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The pathogenesis of Alzheimer's disease is characterized by aggregation of the amyloid-β protein (Aβ) into neurotoxic plaques. Recent in vivo studies have suggested the non-proteolytic clearance of Aβ via receptor-mediated transport across the blood-brain barrier (BBB). The aim of this study was to investigate the role of P-glycoprotein (Pgp) and the low-density lipoprotein receptor-related protein (LRP) in Aβ efflux across the BBB. We developed an in vitro BBB-like model using Madin-Darby Canine Kidney (MDCK) cells seeded on filters separating apical (blood) and basolateral (brain) compartments. MDCK cells were stably transfected with Pgp or mLRP4, an LRP mini-receptor. When compared to empty vector-transfected cells, MDCK-Pgp cells did not transcytose radiolabeled Aβ in the basolateral-to-apical direction. MDCK-mLRP4 cells were found to endocytose and degrade, but not to trasncytose intact radiolabeled Aβ. These results implicate LRP as a mediator of Aβ degradation, but indicate that overexpression of LRP or Pgp alone is insufficient for non-proteolytic transcytosis of intact Aβ.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalNeurobiology of Disease
Volume30
Issue number1
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

Lipoprotein Receptors
Transcytosis
Madin Darby Canine Kidney Cells
P-Glycoprotein
Endocytosis
Blood-Brain Barrier
Amyloid
Peptides
Proteins
LDL-Receptor Related Proteins
Serum Amyloid A Protein
LDL Receptors
Alzheimer Disease
In Vitro Techniques
Brain

Keywords

  • Alzheimer's disease
  • Amyloid-β protein
  • Blood-brain barrier
  • Low-density lipoprotein receptor-related protein
  • MDCK cells
  • P-glycoprotein

ASJC Scopus subject areas

  • Neurology

Cite this

LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-β peptide in a blood-brain barrier in vitro model. / Nazer, Babak; Hong, Soyon; Selkoe, Dennis J.

In: Neurobiology of Disease, Vol. 30, No. 1, 04.2008, p. 94-102.

Research output: Contribution to journalArticle

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