Effect of Presenilin 1 Missense Mutation and Aluminum on Early Neuronal Development of the Mouse Brain

Background: The pathology of Alzheimer's disease (AD) has not been fully elucidated. Presenilin 1 (PS1) mutation is one of the major genetic factors of AD, while aluminum is a candidate for the environmental risk factor. Methods: First, we investigated the influence of PS1 mutation on the neuronal development in ‘knock-in’ mice of PS1 1213T mutation. Next, the effect of prenatal exposure to aluminum on the neuronal development of the knock-in mice was examined. Results: In the newborns with the mutated PS1 allele, a tendency of delayed neurological development was seen and an abnormal distribution of neurofilaments was found, implying that the PS1 mutation might alter early neuronal development. Intraperitoneal administration of aluminum-maltol resulted in the increase of aluminum in brain tissues of newborns, and in abnormal distribution of neurofilaments. Furthermore, the PS1 mutation promoted a change in neurofilament distribution induced by exposure to aluminum. Conclusion: Thus, PS1 mutation and aluminum are suggested to affect early neuronal development, as reflected in some aspects of the pathology of AD.