AI Article Synopsis
- - BACE1 is an important enzyme in the production of amyloid-β, linked to Alzheimer's disease, but trials with BACE1 inhibitors show negative side effects like brain shrinkage and cognitive decline, indicating its role is complex.
- - Research on cerebrospinal fluid (CSF) from a study cohort revealed that higher levels of BACE1 and its product sAPPβ are correlated with the presence of amyloid-β and cortical thickness, but not with amyloid deposits detected via imaging.
- - Interestingly, individuals with higher starting levels of BACE1 had slower brain volume reduction and cognitive decline, suggesting that higher BACE1 activity could be linked to better neuronal health rather than promoting amyloid accumulation.
Article Abstract
Β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) is a crucial protease in the production of amyloid-β (Aβ) in Alzheimer's disease (AD) patients. However, the side effects observed in clinical trials of BACE1 inhibitors, including reduction in brain volume and cognitive worsening, suggest that the exact role of BACE1 in AD pathology is not fully understood. To further investigate this, we examined cerebrospinal fluid (CSF) levels of BACE1 and its cleaved product sAPPβ that reflects BACE1 activity in the China Aging and Neurodegenerative Disorder Initiative cohort. We found significant correlations between CSF BACE1 or sAPPβ levels and CSF Aβ40, Aβ42, and Aβ42/Aβ40 ratio, but not with amyloid deposition detected by 18F-Florbetapir PET. Additionally, CSF BACE1 and sAPPβ levels were positively associated with cortical thickness in multiple brain regions, and higher levels of sAPPβ were linked to increased cortical glucose metabolism in frontal and supramarginal areas. Interestingly, individuals with higher baseline levels of CSF BACE1 exhibited slower rates of brain volume reduction and cognitive worsening over time. This suggests that increased levels and activity of BACE1 may not be the determining factor for amyloid deposition, but instead, may be associated with increased neuronal activity and potentially providing protection against neurodegeneration in AD.
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Article Synopsis
- The study investigates the potential of cerebrospinal fluid (CSF) biomarkers, particularly neurogranin and BACE1, to predict cognitive decline in individuals with subjective cognitive decline (SCD) before developing Alzheimer's disease (AD).
- Researchers analyzed data from 530 participants and found that higher levels of neurogranin and its ratio to BACE1 were linked to faster cognitive decline and increased risk of progressing from SCD to mild cognitive impairment (MCI).
- The findings suggest that monitoring neurogranin levels could help in identifying those at greater risk for cognitive decline, potentially aiding in earlier diagnosis and intervention for Alzheimer's disease.
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