APOE and Senile plaques: For example, the presence of the APOE ε4 allele increases the production of β-amyloid (the main constituent of the senile plaques in AD) in cultured hippocampal neurons [99], reduces synaptic plasticity in the hippocampus [100], promotes β-amyloid induced blockade of plasticity in the hippocampus [101] and impairs hippocampus-dependent spatial memory [102,103].