Amyloid beta-protein (Aβ) increases apolipoprotein E (apoE) levels in astrocytes which could alter lipid trafficking. The mechanism for the Aβ-induced increase in apoE levels is not well understood. It is well established that stimulation of β-adrenergic receptors (βARs) increases cAMP levels. Elevation of cAMP levels increases apoE abundance. The current study determined if Aβ1-42 stimulation of cAMP and apoE levels could be inhibited by βAR antagonists in astrocytes. We demonstrate that Aβ1-42 but not the reverse protein Aβ42-1 or Aβ1-40 stimulated cAMP formation and this stimulation was inhibited by selective βAR antagonists in mouse primary cortical astrocytes. Aβ1-42 significantly increased apoE levels which were significantly inhibited by the βAR selective antagonists with the greatest inhibition observed with the β2 antagonist. Separate lines of evidence have suggested that agonist-induced stimulation of βARs and increases in apoE abundance may serve a neuroprotective role in astrocytes. Our results indicate a potential interaction between βARs and apoE which may contribute to reducing Aβ1-42 neurotoxicity.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Oct 27 2006|
Bibliographical noteFunding Information:
This work was supported by grants from the National Institutes of Health AG-23524, AG-18357 and resources/facilities of the Minneapolis VA Medical Center.
Copyright 2008 Elsevier B.V., All rights reserved.
- Alzheimer's disease
- amyloid beta-protein
- apolipoprotein E
- beta-adrenergic receptors