• secondary structure;
  • Alzheimer's disease;
  • DNA laddering;
  • caspase-3


The Dutch (E22Q) and Flemish (A21G) mutations in the βAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three Aβ(12–42) variants [wild-type (WT), Dutch and Flemish] were tested. At a concentration of 5 µm the aggregation of these peptides followed the order: Aβ(1–42) WT > Aβ(12–42) WT > Aβ(12–42) Flemish > Aβ(12–42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their α-helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in β-sheet and random coil content. Apoptosis was induced in neuronal cells by the Aβ(12–42) WT and Flemish peptides at concentrations as low as 1–5 µm, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase-3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N-truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length Aβ(1–42) peptide was weaker than that induced by its N-truncated variant. These data suggest that N-truncation enhanced the cytotoxic effects of Aβ WT and Flemish peptides, which may play a role in the accelerated progression of dementia.