Deposition of Alzheimer's β-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans

Silke Vogelgesang, Ingolf Cascorbi, Eike Schroeder, Jens Pahnke, Heyo K. Kroemer, Werner Siegmund, Christiane Kunert-Keil, Lary C. Walker, Rolf W. Warzok*

*Corresponding author for this work
274 Citations (Scopus)


Deposition of the β-amyloid peptide (Aβ) in the brain occurs during normal ageing and is substantially accelerated in patients with Alzheimer's disease. Since Aβ is continuously produced in the brain, it has been suggested that a clearance mechanism should exist to prevent its accumulation and subsequent aggregation. Until now, little attention has been paid to the possible role of P-glycoprotein (P-gp), a member of the ATP binding cassette superfamily of transporter proteins, in the pathogenesis of Alzheimer's disease. A recent study demonstrated in vitro that Aβ40 and Aβ42 interact directly with P-gp. We therefore hypothesized that Aβ accumulation in the brain would correlate inversely with the degree of vascular P-gp expression. To study early pathogenetic factors that influence the deposition of Aβ, at routine autopsies, brain tissue samples were taken from 243 non-demented subjects who died between the ages of 50 and 91 years. Vascular P-gp expression and the number of Aβ40- and Aβ42-positive senile plaques were assessed immunohistochemically in the medial temporal lobe. In addition, the apolipoprotein E (apoE) genotypes, as well as multiple drug resistance gene 1 (MDR1) polymorphisms (exon 2, G-1A; exon 21, G2677T/A; exon 26, C3436T), were also determined for each case. P-gp expression was not correlated with MDR1 genotypes, but we found a significant inverse correlation between P-gp expression and the deposition of both Aβ40 and Aβ42 in the medial temporal lobe. Our results provide the first evidence in human brain tissue that the accumulation of Aβ may be influenced by the expression of P-gp in blood vessels, and suggest that P-gp may influence the elimination of Aβ from brain.

Original languageEnglish
Issue number7
Pages (from-to)535-541
Number of pages7
Publication statusPublished - 10.2002

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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