Upregulation of Presenilin 1 in Brains of Sporadic, Late-Onset Alzheimer's Disease

The activity of the β-secretase involved in the cleavage of amyloid-β (Aβ) is increased in sporadic late-onset Alzheimer's disease (AD). Whether the corresponding γ-secretase activity is altered is still uncertain. We evaluated mRNA expression and protein levels of presenilin 1 (PS1) and γ-secretase activity in the frontal cortex of 32 cases with late-onset sporadic AD and those of 29 control subjects. We found a significant increase in PS1 mRNA, protein levels and γ-secretase activity in AD cases. These findings suggest that upregulation of PS1 leads to Aβ overproduction and accumulation in sporadic AD.