Reduced Influence of apoE on A β43 Aggregation and Reduced Vascular Aβ43 Toxicity as Compared with Aβ40 and Aβ42

AbstractThe amyloid- β 43 (Aβ43) peptide has been shown to be abundantly expressed in Alzheimer’s disease plaques, whereas only relatively low levels have been demonstrated in cerebral amyloid angiopathy (CAA). To better understand this discrepant distribution, we studied various biochemical properties of Aβ43, in comparison with Aβ40 and Aβ42. We assessed the interaction of Aβ43 with the three apoE isoforms (apoE2, apoE3, and apoE4) using SDS-PAGE/Western blotting and ELISA, aggregation propensity using thioflavin T assays, and cytotoxicity towards cerebrovascular cells using MTT assays. We found that Aβ 43 did not differ from Aβ42 in its interaction with apoE, whereas Aβ40 had a significantly lower degree of interaction with apoE. At a molar ratio of 1:100 (apoE:Aβ), all apoE isoforms were comparably capable of inhibiting aggregation of Aβ40 and Aβ42, but not Aβ43. All Aβ variants had a conc entration-dependent negative effect on metabolic activity of cerebrovascular cells. However, the degree of this effect differed for the three Aβ isoforms (Aβ40 >  Aβ42 >  Aβ43), with Aβ43 being the least cytotoxic peptide towards cerebrovascular cells. We conclude that Aβ43 has different biochemical characteristics compared with Aβ40 and Aβ42. Aggregation of Aβ43 is not inhibited by apoE, in contrast to the aggregation of Aβ40 and Aβ42. Furthermore, cerebr ovascular cells are less sensitive towards Aβ43, compared with Aβ40 and Aβ42. In contras...

Source: Molecular Neurobiology - January 16, 2020 Category: Neurology Source Type: research