Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins

In the citing paper

“However, recent in vivo studies have shown that soluble Aβ oligomers are more neurotoxic than amyloid plaques and most likely responsible for synaptic dysfunction and memory loss in AD.7–11”

In the citing paper

“However, recent in vivo studies have shown that the soluble Aβ oligomers are possibly more neurotoxic than amyloid plaques,14–17 and are likely responsible for synaptic dysfunction and memory loss in AD patients and AD animal models.18–21”

In the citing paper

“recent studies have shown that the soluble Aβ oligomers are more neurotoxic both in vitro and in vivo.5−8”

In the citing paper

“For the preformed Aβ42 fibrils, no significant cell toxicity was observed in either the absence or presence of Cu2+ (Figure 9, lanes 1 and 2), supporting the previously reported diminished toxicity of Aβ42 fibrils.5,7,54−56”

In the citing paper

“This function may be critical in controlling Aβ deposition as well as levels of potentially neurotoxic Aβ oligomers (Lambert et al., 1998).”

In the citing paper

“While Aβ disrupts synaptic transmission 32,34,35 and induces synapse loss 17”

In the citing paper

“In vitro, apoE and apoJ form stable complexes with A␤ (11, 16 -20), alter the aggregation of various A␤ peptides (21)(22)(23), and affect A␤ neurotoxicity (24 -27).”

In the citing paper

“A␤ 1-42 aged according to this protocol is a mixture of fibrils and soluble globular aggregates, and is active to astrocytes (37,38) and toxic to neurons (26,27).”

In the citing paper

“ApoJ has been shown to potentiate the formation of a neurotoxic species of A␤ (26,27).”

In the citing paper

“ApoE, apoJ, and most recently ␣ 2 -macroglobulin have been shown to form a complex with A␤ that may facilitate clearance of the peptide (25-27, 50, 51).”

In the citing paper

“Evidence suggests that increased uptake of these neurotoxic Aβ42 peptides results in accumulation and aggregation within neurons eventually leading the formation of plaques and neuronal death [40, 41].”

In the citing paper

“Most importantly, these amyloid-free Aβ oligomers were potent CNS neurotoxins.”

In the citing paper

“With chronic exposure, neurons ultimately were killed. Death was selective for subpopulations of vulnerable neurons and was prevented by knockout of Fyn, a protein tyrosine kinase linked to NMDA receptor signaling.”

In the citing paper

“Investigation into the action of clusterin by Lambert, Klein and colleagues established that, concomitant with inhibition of amyloid formation, clusterin promotes accumulation of soluble Aβ oligomers (Lambert et al., 1998).”

In the citing paper

“oligomers were found to inhibit functional synaptic plasticity (Lambert et al., 1998). Long-term potentiation (LTP) was inhibited within minutes. This rapid loss of LTP, measured in rat brain slices and in situ in mice, occurred without impact on baseline excitability, indicating impairment of signaling rather than degeneration.”

In the citing paper

“In hippocampal slices, synthetic oligomers cause rapid LTP inhibition (Barghorn et al., 2005; Fa et al., 2010; Jurgensen et al., 2011; Lambert et al., 1998; Nimmrich et al., 2008; Rammes et al., 2011; Wang et al., 2002).”

In the citing paper

“early studies showed that binding is lost upon controlled trypsin treatment of neurons (Lambert et al., 1998).”

In the citing paper

“In vitro and in vivo studies have now indicated that soluble Aβ oligomers impair synaptic plasticity, inhibiting hippocampal long-term potentiation (LTP), the electrophysiological correlate of learning and memory (3 –6).”