Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cerebral accumulation of extracellular amyloid β
(Aβ) and neurofibrillary tangles made of hyperphosphorylated tau protein, two main lesions which appear sequentially during the disease
progression. In the last decade numerous studies have proposed small soluble aggregates of Aβ, known as oligomers, as the species responsible
for synaptic dysfunction, memory loss and neurodegeneration typical of AD. In vitro and in vivo experiments have identified
Aβ oligomers as the elements that can alter synaptic function by a reversible mechanism, which gradually becomes permanent when exposure
is continuous. Here we show that intracerebroventricular (ICV) injection in mice of a solution containing specifically Aβ1-42 oligomers
substantially affects their memory when tested in the novel object recognition task. This acute mouse model enabled us to distinguish
whether oligomers were affecting specific phases of the memory processing. A single injection of Aβ1-42 oligomers before memory
consolidation abolished information processing, leading to memory impairment, whereas no such effects were observed when the injection
was done once the information had been processed, indicating that the oligomers affect memory consolidation rather than retrieval.
Beside Aβ1-42, Aβ1-40 oligomers also impaired memory, and both isoforms were antagonized by the anti-A β4G8 monoclonal antibody.
This simple and reliable paradigm is useful to investigate the mechanisms through which Aβ oligomers interfere with neuronal processes
and to test the efficacy of new therapeutic approaches specifically against these species. We tested several molecules by direct coincubation
with Aβ oligomers, ICV injections preceding Aβ oligomers, and the systemic treatment with drugs that cross the blood brain
barrier. We also examined the proposed involvement of cellular prion protein as a mediator of the oligomer-induced memory impairment.