Abstract WP555: Plasma Beta-Secretase 1 in Cerebral Amyloid Angiopathy

Abstract

Backgrouds: Beta-secretase 1 (BACE1) is the rate-limiting enzyme in amyloidogenesis. We have recently reported that plasma BACE1 activity may predict Alzheimer’s disease as surrogate biomarkers, and BACE1 protein and activity levels are increased in cortical vessels from patients with cerebral amyloid angiopathy (CAA). However, little is known about the plasma BACE1 levels in CAA. Methods: A single-center prospective cohort of probable CAA patients admitted to Huashan Hospital from December 2014 to September 2017 were age, sex and education matched with elder adults from population-based Shanghai Aging Study cohort. We collected the clinical data, plasma and imaging markers. We measured plasma BACE1 concentration with our in house ELISA and BACE1 activity as we recently described. BACE1 concentration and activity were compared between CAA and controls and within CAA patients according to disease severity using generalized linear models. Results: There were 40 CAA patients with mean age of 73.3 years and 41 controls of 72.8 years. Compared with heathy controls, CAA patients showed a higher BACE1 protein concentration (5.44 [3.39, 9.17] ng/ml vs. 7.37 [5.38, 11.88] ng/ml, p=0.009), higher BACE1 activity (218.8±96.0 mFU/min vs. 285.7±119.4 mFU/min, p=0.007) and higher BACE1 activity per total plasma protein (6.99.0±3.07 mFU/min vs. 9.01±4.27 mFU/min, p=0.017), with no significant differences in BACE1 activity-to-concentration ratio (32.46 [20.11, 70.46] vs. 34.27 [17.23, 54.12], p=0.484). A cutoff value of BACE1 activity 252.6 mFU/min was determined to differentiate CAA from healthy elders with a sensitivity of 0.575 and a specificity of 0.683. For CAA patients, plasma BACE1 activity was higher in the severe group (total SVD score ≥4, n=10, 371.62±110.09 mFU/min) than in the mild group (total SVD score <4, n=30, 257.04±109.61 mFU/min, p=0.012). No significant differences were found in CMBs>10 vs. CMBs≤10 group (p=0.600). Conclusions: Plasma BACE1 concentration and activity are increased in CAA patients. Our results indicate that plasma BACE1 may be a promising biomarker for CAA diagnosis and have potential values in disease severity grading. A larger CAA cohort has been recruited to further validate the results.