Our results are in agreement with the findings of early activation of ERK in some neurodegenerative diseases: phosphorylated ERK immunoreactivity has been found in neurons in Pick's disease and progressive supranuclear palsy and corticobasal degeneration (Ferrer et al.,2001), in hippocampal neurons with neurofibrillar degeneration in Alzheimer's disease (AD; Perry et al.,1999), and in astrocytes from early AD patients (Webster et al.,2006). Here, MAPK1 is linked to early-onset autosomal dominant Alzheimer disease.