This study aims to investigate the relationship between plasm β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cerebral small vascular disease (CSVD) in community population.

Nine hundred and one stroke-free participants with brain magnetic resonance imaging from Shuyi community cohort were included (age 55.2±8.72 years, 67.5% female). BACE1 concentration was measured using Human BACE1 Duoset ELISA kit (DY931, R&D system) and activity was measured by a synthetic APPsw polypeptide substrate. CSVD markers included lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMB) and brain atrophy. WMH was quantitatively analyzed by automatic segmentation volume, and whole brain atrophy was represented by brain parenchymal fraction (BPF). Moreover, atrophy of gray matter, white matter, cortex and hippocampus was further analyzed by the volume ratio of specific brain regions. BACE1 concentration and activity are naturally logarithmic to satisfy the normal distribution.

Plasma BACE1 concentration and activity was 4.46 (2.89-6.93) ng/ml and 344.19 (249.7-437.41) RFU/min respectively. After adjusting for age, sex and ApoE4, BACE1 concentration was significantly negatively correlated with BPF (β±SE -0.096±0.002, p=0.008) and white matter volume ratio (β±SE -0.137±0.001, p=0.001). The above associations persisted after adjusting for cerebrovascular disease risk factors. There was no significant correlation between BACE1 concentration and lacunes, WMH, CMB. There was no significant relationship between BACE1 activity and CSVD markers.

The effect of BACE1 on brain structure may be more prominent than that on vessels. BACE1 mainly affects white matter structure in the early stage by concentration, but not the activity.