Aβ oligomers inhibit synapse remodelling necessary for memory consolidation.

Extensive research has implicated the amyloid-β protein (Aβ) in the aetiology of Alzheimer's disease (AD). This protein has been shown to produce memory deficits when injected into rodent brain and in mouse models of AD Aβ production is associated with impaired learning and/or recall. Here we examined the effects of cell-derived SDS-stable 7PA2-derived soluble Aβ oligomers on consolidation of avoidance learning.

A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease.

Objective: To examine in vivo levels of beta-amyloid (Abeta) oligomers (oAbeta) vs monomeric Abeta in plasma and brain tissue of patients with sporadic and familial Alzheimer disease (AD) using a new enzyme-linked immunosorbent assay (ELISA) specific for oAbeta.

Design: To establish the oAbeta ELISA, the same N-terminal Abeta antibody was used for antigen capture and detection. Plasma and postmortem brain tissue from patients with AD and control subjects were systematically analyzed by conventional monomeric Abeta and new oAbeta ELISAs.

Intracerebroventricular Administration of Amyloid β-protein Oligomers Selectively Increases Dorsal Hippocampal Dialysate Glutamate Levels in the Awake Rat.

Extensive evidence supports an important role for soluble oligomers of the amyloid β-protein (Aβ) in Alzheimer's Disease pathogenesis. In the present study we combined intracerebroventricular (icv) injections with brain microdialysis technology in the fully conscious rat to assess the effects of icv administered SDS-stable low-n Aβ oligomers (principally dimers and trimers) on excitatory and inhibitory amino acid transmission in the ipsilateral dorsal hippocampus. Microdialysis was employed to assess the effect of icv administration of Aβ monomers and Aβ oligomers on dialysate glutamate, aspartate and GABA levels in the dorsal hippocampus.

Soluble amyloid-beta peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo.

Long before the onset of clinical Alzheimer's disease non-fibrillar, soluble assembly states of amyloid-beta (Abeta) peptides are believed to cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Since many of the risk factors for Alzheimer's disease are vascular, impairment of cerebral blood flow by soluble Abeta has been proposed to be critical in triggering these early changes. However, it is not known if soluble Abeta can affect cerebrovascular function at the concentrations required to cause inhibition of synaptic plasticity mechanisms believed to underlie the early cognitive deficits of Alzheimer's disease.