Romberg, C., McTighe, S.M., Heath, C.J., Whitcomb, D., Cho, K., Bussey, T.J. & Saksida, L.M. (2012) False recognition in a mouse model of Alzheimer’s disease: rescue with sensory restriction and memantine. Brain, in press.
Alzheimer’s disease is commonly regarded as a loss of memory for past events. However, patients with Alzheimer’s disease seem not only to forget events but also to express false confidence in remembering events that have never happened. How and why false recognition occurs in such patients is currently unknown, and treatments targeting this specific mnemonic abnormality have not been attempted. Here, we used a modified object recognition paradigm to show that the tgCRND8 mouse—which overexpresses amyloid b and develops amyloid plaques similar to those in the brains of patients with Alzheimer’s disease— exhibits false recognition. Furthermore, we found that false recognition did not occur when tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling previous findings in patients with mild cognitive impairment, which is often con- sidered to be prodromal Alzheimer’s disease. Additionally, false recognition did not occur when mice were treated with the partial N-methyl-D-aspartic acid receptor antagonist memantine. In a subsequent experiment, we found abnormally enhanced N-methyl-D-aspartic acid receptor-dependent long-term depression in these mice, which could be normalized by treatment with memantine. We suggest that Alzheimer’s disease typical amyloid b pathology leads to aberrant synaptic plasticity, thereby making memory representations more susceptible to interfering sensory input, thus increasing the likelihood of false recogni- tion. Parallels between these findings and those from the literature on Alzheimer’s disease and mild cognitive impairment suggest a mechanism underlying false recognition in these patients. The false recognition phenomenon may provide a novel paradigm for the discovery of potential therapies to treat the mnemonic dysfunction characteristic of this disease.