Figure 3

Aβ immunostainings of Sw2 patient’s frontal and temporal cortex and mass spectra of Aβ peptides in Sw2 patient’s temporal cortex. a: Confocal micrograph from Sw2 patient’s temporal cortex shows the targetoid pattern of the plaque: the corona contains Aβ_x-42 and the centre Aβ_1-5 species. b: The central accentuation of abAβ_arc (specific for the Arctic mutation) immunopositivity suggests that much of the mutated Aβ has preserved N-termini (Sw2, frontal cortex; see Figure 2g and h). c and d: Pyroglutamate specific abAβ_3pE and abAβ_11pE antibodies demonstrate that much of the Aβ is truncated and glutamates 3 and 11 are cyclised into pyroglutamate and this modification occurs in parallel at both sites. Note the strong positivity in pial arteries (Sw2, temporal cortex, consecutive sections). e: Average mass spectra of Aβ peptides extracted from Sw2 patient’s temporal cortex with formic acid and immunoprecipitated with abAβ_17–24 and abAβ_Arc (conformation specific epitope 17-24arc), which precipitate both wild type Aβ and Arctic Aβ (see inserted cartoon). Three peaks corresponding to arcAβ species (with the Arctic mutation) and recognized by Aβ_pE specific antibodies (values observed in two independent MALDI-TOF experiments m/z=3061.5 and m/z=3062.8 Da → Aβ11pE-40arc; m/z=3246.2 and m/z=3246.0 Da → Aβ11pE-42arc; m/z=4057.0 Da → Aβ3pE-40arc) as well as two peaks corresponding to arcAβ with full length N-termini (m/z=4258.7 and m/z= 4259.1 Da → 1-40arc; m/z=4443.5 and m/z=4443.0 Da → 1-42arc) are labelled. Additional values with relative intensities of the peaks, see Additional file 5: Table S1. (bar in a 50 μm; bar in b 200 μm for b-d).