Figure 4.

SEC-isolated Aβ oligomers, but not monomers, inhibit LTP. A, 7PA2 cells were allowed to condition serum-free medium in the presence or absence of RS-0406 or RS-0466 for 15 h, and the CM was concentrated as described. The concentrated CM was subjected to SEC, and fractions were analyzed by Western blotting using a combination of 2G3 and 21F12. Aβ monomers (M), dimers (D), and trimers (T) are indicated by arrows. B, SEC fractions containing monomeric or oligomeric Aβ were lyophilized and reconstituted in 10 ml of ACSF, and an aliquot (1.5 ml) was analyzed by IP/Western blot. C, Perfusion of hippocampal slices with oligomeric Aβ (fraction 7) inhibited LTP (115.8 ± 10.0% at 60 min post-HFS; mean ± SEM percentage of baseline; n = 6; p > 0.05 compared with pre-HFS baseline), whereas perfusion with monomeric Aβ (fraction 9) did not alter LTP (227.1 ± 22.6% at 60 min post-HFS; mean ± SEM percentage of baseline; n = 6; p > 0.05 compared with pre-HFS baseline). Insets show typical EPSPs ∼5 min pre- (1) and ∼60 min post-HFS (2). Calibration: 25 ms, 2 mV. Arrows signify the period of HFS, and the asterisk indicates addition of test media.