Serum β-secretase 1 (sBACE1) activity in subjective cognitive decline: an exploratory study

Area of Science:

• Neuroscience
• Biochemistry
• Biomarker Discovery

Background:

• Beta-secretase-1 (BACE1) is crucial for amyloid-beta homeostasis and implicated in Alzheimer's disease pathogenesis.
• Increased serum BACE1 (sBACE1) activity is a potential early biomarker for Alzheimer's disease.
• Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia.

Purpose of the Study:

• To investigate if sBACE1 activity increases in individuals with SCD.
• To compare sBACE1 activity in SCD, MCI, and cognitively normal individuals.
• To explore potential sex differences in sBACE1 activity across cognitive states.

Main Methods:

• Serum BACE1 activity was measured in individuals with SCD (n=118), amnestic MCI (n=179), non-amnestic MCI (n=99), and cognitively normal controls (n=137).
• Statistical analyses were performed to compare sBACE1 activity between groups, adjusting for age, sex, and comorbidities.
• Sexual dimorphism in sBACE1 activity was assessed.

Main Results:

• sBACE1 activity was significantly higher in individuals with SCD compared to controls (p < 0.001).
• sBACE1 activity was significantly higher in both amnestic MCI (p < 0.001) and non-amnestic MCI (p = 0.02) groups compared to SCD.
• Women with MCI showed higher sBACE1 activity than men, a dimorphism not observed in SCD.

Conclusions:

• Increased sBACE1 activity is present in early stages of cognitive decline, including SCD.
• sBACE1 activity shows potential as a blood-based screening tool for individuals at risk of MCI and dementia.
• Findings highlight the role of BACE1 in early cognitive impairment and suggest sex-specific differences in MCI.