β-Secretase-1 (BACE1) plays a key role in the regulation of cerebral amyloid-β homeostasis, being involved in amyloidogenic and, as recently found, amyloidolytic pathways. Growing evidence indicates t Show more
β-Secretase-1 (BACE1) plays a key role in the regulation of cerebral amyloid-β homeostasis, being involved in amyloidogenic and, as recently found, amyloidolytic pathways. Growing evidence indicates that increased serum BACE1 (sBACE1) activity might represent an early biomarker for Alzheimer's disease. Here, we tested the hypothesis that an increase in sBACE1 activity may already occur in individuals with subjective cognitive decline (SCD). We found that sBACE1 activity was significantly higher in individuals with SCD (n 118) compared to cognitively normal subjects (controls, n 137) (p < 0.001). Moreover, compared with SCD, sBACE1 activity was even higher in patients affected by amnestic (n 179) or non-amnestic mild cognitive impairment (MCI) (n 99) (p < 0.001 and p 0.02, respectively). In all cases, the respective increase in sBACE1 activity was significant after adjustment for possible confounders including age, sex, and comorbidities. We also found a significant sexual dimorphism, with women affected by either type of MCI, but not by SCD, having higher levels of serum BACE1 activity compared to men. These results provide evidence supporting the potential use of sBACE1 activity as tool for blood-based screening of cognitively healthy individuals at clinical risk of MCI and dementia. Show less
Increasing evidence indicates that β-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and Show more
Increasing evidence indicates that β-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. prospective analysis of serum samples, clinical, biological, and demographic variables. Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. Age was the strongest independent predictor of sBACE1 variance (β=0.425, p<0.0001), followed by sex (β=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (β=-0.168, p<0.0001) and hypertension (β=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age. Show less