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. 2006 Oct 11;26(41):10536–10541. doi: 10.1523/JNEUROSCI.3133-06.2006

Figure 2.

Figure 2.

Intraneuronal accumulation of Aβ in p25 Tg mice in perinuclear pools. a, Increased 4G8 immunoreactivity was found in cell bodies of the cortex of CK–p25 mice compared with WT controls at 8 weeks of induction. b, Intraneuronal Aβ accumulation was detected by 6E10 and M1 antibodies. APP holoprotein levels, as detected by the R1736 APP N-terminal antibody, were similar between CK–p25/PD-APP and PD-APP mice. Cortex of mice induced for 8 weeks are shown. c, Immunoelectron microscopy with the 4G8 antibody demonstrate the aggregation of intraneuronal Aβ in fibril-like structures adjacent to the nucleus in CK–p25 mice (middle, arrows), which were more extensive and frequent in CK–p25/PD-APP mice (right, arrows). Also shown is a neuron without 4G8 immunoreactivity (left). Inset is a magnification of the area outlined by the smaller box. d, First panel, Perinuclear Aβ aggregates were also immunoreactive toward NF-H (smaller immunogold particles) and 4G8 (larger particles). In the CK–p25/PD-APP mice, aggregates stained positive for the Aβ-related antibodies 6E10 (second panel), M1 (third panel), and R1282 (fourth panel). Nuclear area (e) and percentage occupied by condensed chromatin (f) were calculated for neurons without (n = 16; blue squares) and with (n = 13; red triangles) perinuclear Aβ aggregations from immunoelectron micrographs from CK–p25/PD-APP mice. Results are displayed as a scatter plot, with error bars indicating SEM. Results were statistically significant (p = 0.0011 for e; p = 0.0002 for f) according to two-tailed, unpaired Student's t test. For c and d, immunoelectron microscopy was performed on 12 week induced CK–p25 and CK–p25/PD-APP mice, analyzing the subiculum region, which showed the greatest 4G8 staining (data not shown). Scale bar, 500 nm. g, Cortical neurons from 5–10 week CK–p25/PD-APP mice (n = 3) expressing p25–GFP with or without intraneuronal 6E10 staining were scored in a blinded manner for degenerative nuclear morphology, as indicated by condensed or invaginated nuclei. A minimum of 200 6E10-positive and 200 6E10-negative neurons were counted for each animal. Shown in the left are an example p25-positive, 6E10-positive neuron and a p25-positive, 6E10-negative neuron; the right indicates total quantification. DAPI, 4′,6′-Diamidino-2-phenylindole.