Figure 3

Amyloid beta peptide is (synapto)toxic over a wide range of sizes. (a) Lipid-derived amyloid beta peptide (Aβ) oligomers cause learning and memory impairments in mice. Passive avoidance test of mice injected with backward protofibrils. Light-dark step through test showed latency of entrance during the training accompanied with electrical shock (white bars) and during the testing 24 hours later (black bars). Injection of Aβ fibrils/brain total extract (BTE) mixture-soluble fractions 1.5 hours before the shock impaired memory in contrast to groups injected with control vehicle. From Martins and colleagues [59]. (b). Soluble Aβ extracted from Alzheimer's disease (AD) brain alters hippocampal synapse physiology and learned behaviour. Rats receiving AD Tris-buffered saline (TBS; dashed line) had a significantly shorter mean escape latency than animals receiving immunodepleted AD TBS (continuous line) at 48 hours after training. From Shankar and colleagues [11]. (c) Effects of purified brain Aβ*56 (soluble Aβ species with an apparent molecular weight of 56 kDa) on memory of young rats. Aβ*56 impairs spatial memory. Rats that received vehicle but not Aβ*56 injections showed a significant spatial bias for the escape location 24 hours after training [14]. (d) Vulnerability of NT2 cells to soluble oligomeric Aβ in vitro. The ability of cells to oxidize MTT was used as a measurement of cell viability after treatment with Aβ. Cells were incubated in the presence of different concentrations of either Aβ or equivalent amounts of dimethyl sulfoxide (DMSO) control for 20 hours. The x-axis represents the concentration of soluble oligomeric Aβ. The y-axis represents the percentage of viability of cells compared with the DMSO control. From Kim and colleagues [68]. (e) Human cerebrospinal fluid (huCSF) containing clearly detectable Aβ dimers disrupts synaptic plasticity in vivo. Samples of huCSF containing Aβ dimers (huCSF D) completely inhibited long-term potentiation, and this inhibition was prevented by previous immunodepletion of Aβ. Untreated huCSF (open circles), and immunodepleted samples (filled circles) were injected 10 minutes before high-frequency stimulation (arrow). From Klyubin and colleagues [10]. ADDL, Aβ-derived diff usible ligand; EPSP, excitatory postsynaptic potential.