The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease

We evaluated expression, protein levels and activity of the β-site cleaving enzyme (BACE1) as well as the amount of products of lipid peroxidation in frontal cortex of three groups of cases: sporadic Alzheimer's disease (AD); control subjects (CTR); cognitively normal subjects with abundant amyloid plaques (NA). We found a significant increase of BACE1 activity and products of lipid peroxidation in brain tissue of AD cases, with normal gene expression, and non-significant elevation of protein levels. CTR and NA samples showed similar levels of BACE1 activity and oxidative products. BACE1 activity and the amount of oxidative products were significantly correlated in all cases. Moreover, both BACE1 activity and the level of 4-hydroxynonenal were correlated with the amount of β-amyloid pyroglutamated 3-42, the more toxic β-amyloid peptide that is characteristic of AD. These findings suggest that BACE1 activity reflects the type of Aβ species, rather than the β-amyloid plaques load. Hence, the increase of BACE1 activity occurring in sporadic AD is likely the effect, rather the cause, of Aβ accumulation and oxidative stress.