We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Aβ) peptide formation in primary chicken telencephalic neurons, because their Aβ peptide sequence is identical to humans. As detected by quantitative Aβ-SDS-PAGE/immunoblot, Aβ peptides 1–40/42 and three additional C-truncated species, namely Aβ1–37/38/39 were regularly released into the supernatant. The highly conserved Aβ quintet strongly resembles the pattern of Aβ peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Aβ peptides 1–33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Aβ1–42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Aβ peptide secretion as well as intracellular Aβ peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Aβ1–37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Aβ1–38 while Aβ1–40 and Aβ1–42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Aβ peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Aβ1–38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Aβ peptide production.

Keywords:
Telencephalic neurons, chicken, β-Amyloid, Amyloid precursor protein, SELDI
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© 2004 S. Karger AG, Basel
2004
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