Abstract Details

BACE1, as the rate-limiting step in the Aβ production, is considered as a candidate biomarker of Alzheimer's disease (AD) and is also involved in the disruption of cerebral vessels.

The aim of this study was to firstly describe the concentration and activity of plasma BACE1 in a community cohort of China, and to explore its influencing factors and its relationship with plasma Aβ.

887 cognitively healthy subjects form Shunyi cohort were included in this cross-sectional study. We used linear regression analysis to investigate the relationship between the concentration and activity of plasma BACE1 with common AD and vascular disease risk factors, with plasma Aβ42 and Aβ40 concentrations.

The concentration of BACE1 in present study was 4.46(2.89-6.93) ng/ml and the activity was 344.19(249.7-437.41) RFU/min. After adjusting for age, sex, ApoE4 allele, increasing age [β (SE) =0.05 (0.02), p=0.021] and increasing systolic blood pressure [β (SE) =0.03 (0.01), p=0.015] were positively correlated with lnBACE1 activity. lnhsCRP[β (SE) =0.07 (0.02), p=0.001] and lnTNF-α[β (SE) =0.24 (0.08), p=0.002] were positively correlated with lnBACE1 activity. The concentration of lnBACE1 was negatively correlated with the concentration of Aβ42[β (SE) =-0.86 (0.28), p=0.003] and Aβ40[β (SE) =-15.6 (2.13), p < 0.001], while was positively associated with Aβ42/40 [β (SE) =0.10 (0.02), p < 0.001]. There was no significant correlation between lnBACE1 activity and Aβ concentration.

BACE1 activity but not concentration increased with age. Control of systolic blood pressure, screening and intervention of systemic inflammation may reduce BACE1 activity in cognitively normal population. Decreased plasma Aβ42 and Aβ40 concentrations and elevated Aβ42/40 may reflect the early state of cognitive decline caused by neurodegenerative and vascular diseases.