Generation of Aβ species is a hallmark of Alzheimer’s Disease. QPS Neuropharmacology provides several cell culture models to identify pharmacological agents that interfere with the cleavage of APP by analyzing the generation of different Aβ and sAPP species by immunosorbent assay.
- Primary chicken telencephalic neurons secrete endogenous wildtype Aβ peptides, including Aβ38, Aβ40 and Aβ42. Both human and chick Aβ42 are identical in sequence. Therefore, this model is suitable for studying effects on processing of endogenous wildtype APP in primary neurons.
- Primary rat/mouse hippocampal neurons are phenotypically closer to adult neurons as they have extended a dense network of neuronal processes.
- H4 neuroglioma cells overexpressing human APPK595N/M596L, the Swedish double mutation, enable to analyze compounds for their effects on the human mutant APP profile.
Figure: Aβ peptide profile in primary chicken neurons and APPK595N/M596L overexpressing cells.
(A) H4 cells overexpressing human APPK595N/M596L generated more Aβ38, 40, and 42 peptides in 24h than primary chicken neurons determined by an immunosorbent assay. In both, Aβ40 was the predominant Aβ peptide. (B) The γ-secretase inhibitor DAPT reduced Aβ formation in primary chicken neurons and in H4-hAPPK595N/M596L. In the H4 cell line, Aβ levels started to decrease at a concentration of 50nM in H4 cells and at 100 nM DAPT in chicken neurons after 24h treatment.