Synthetic Abeta 1-40 oligomers impair recognition memory in mice

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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. 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. 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. 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.