Development of non-invasive therapeutical strategies to ameliorate memory deficits, synaptic plasticity and neurodegeneration in a comprehensive mouse model of Alzheimer disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by progressive memory deficits and cognitive decline. We explored the possibility that Environmental Enrichment (EE) may reduce the disease progression in a comprehensive mouse model for AD like neurodegeneration, the AD11 mice. AD11 mice, which express anti nerve growth factor (NGF) antibodies, develop an age dependent neurodegeneration which encompasses all hallmarks of human AD. We have tested the efficacy of EE starting from 2 months of age, that is before the onset of behavioural deficits in AD11 mice. At 7 months of age, visual recognition memory was tested with the Object Recognition Test (ORT), spatial memory with the Morris Water Maze (MWM) and the presence of AD pathological hallmarks (Aβ clusters, presence of hyperphosphorylated tau and cholinergic deficit) was assessed immunohistochemically. We found that in AD11 mice exposed to EE from 2 to 7 months of age performance in both memory tests was significantly better than in non EE AD11 mice and indistinguishable from that in wild-type mice of the same age. Exposure to EE from 2 to 7 months significantly reduce the appearance of AD neuropathological hallmarks. A group of AD11 mice was tested also at 12 months of age: we found that 12 months old AD11 mice exposed to EE from 2 to 7 months of age performed significantly better than non EE AD11 mice of the same age and did not differ from 12 months old wt mice. Thus, EE is able to prevent the onset of memory deficits up to at least 12 months of age and to restrain the progression of neurodegeneration in a mouse model of AD. Telethon grant GGP030416