Synthetic Abeta 1-40 oligomers impair recognition memory in mice

Background: Alzheimer disease (AD) is a neurodegenerative pathology characterized by cerebral β-amyloid (Aβ) deposits, neurofibrillary tangles, early synaptic dysfunction and subsequent memory loss. Aβ oligomers, rather than fibrils, were proposed to play a major role in the neurodegeneration. Various forms of Aβ oligomers extracted from the brain were shown to induce synaptic failure and cognitive impairment. Aβ oligomers inhibited the long-term potentiation (LTP) process, a paradigm measuring synaptic plasticity, and induced loss of dendritic spines which represent synaptic connections in the formation of new memory traces. Methods: The present study was aimed to investigate, in vivo, the effect of synthetic Aβ1-40 monomer, small oligomers and higher aggregates, in mice tested in the object recognition task. Aβ oligomers were covalently stabilized using the photo-induced-cross-linking technique. Two hours following Aβ1-40 (1.0 μM) intracerebroventricle (icv) injection, mice underwent to the familiarization phase on day 1 and to the memory test phase on day 2. Memory abilities were determined calculating the discrimination index. Results: Our findings show that only Aβ1-40 oligomers have the ability to impair long-term recognition memory. Moreover, we demonstrated that this effect was reverted by an icv pretreatment with the 4G8 anti-Aβ antibody. Conclusions: Our findings demonstrate, in vivo, that beside Aβ1-42 also synthetic Aβ1-40 oligomers have toxic effects on cognitive processes. Furthermore, the ability of the Aβ specific antibody to revert Aβ1-40-mediated cognitive impairment, supports the immunotherapy as useful strategy in the AD pathology.