Figure 1. Soluble Aβ facilitates long-term depression in the CA1 region of hippocampal slices.

(A) Western blot of the 3 sources of soluble Aβ used for LTD experiments in this study. All 3 contain a SDS-stable band at ∼8 kDa, and this has been confirmed previously as an Aβ dimer by mass spectrometry (Shankar et al, 2008). 7PA2 CM also contains a higher, apparent trimer species. CHO- CM is devoid of these human Aβ species, as expected, and serves as a negative control throughout these studies. All samples were immunoprecipitated with polyclonal Aβ antibody AW8 and blotted with combined Aβ monoclonal antibodies 2G3 (Aβ₄₀) and 21F12 (Aβ₄₂). SEC: fractions rich in oligomers (left) or monomers (right) separated by SEC of 7PA2 CM (B) A train of 300 single pulses at 1 Hz (5 min; small grey bar) did not induce LTD in acute mouse hippocampal slices in the presence of CHO- CM (blue squares, n=6) but induced a significant LTD in the presence of 7PA2 CM (red circles, n=7). C-F A standard LTD protocol of 900 single pulses at 1 Hz (15 min; long grey bar) was applied to slices treated with 7PA2 CM (C), synthetic Aβ_1-42 (D), AD brain TBS extract (E), or SEC fractions from 7PA2 CM (F). All are not significantly different from their respective controls. Insets in B-F represent typical field excitatory postsynaptic potentials (fEPSPs) recorded before (light) and 50 min after (dark) LFS. Horizontal calibration bar, 10 ms; vertical bar, 0.5 mV.