Reduced Levels of Amyloid-β-Binding Proteins in Cerebrospinal Fluid from Alzheimer's Disease Patients

Abstract

Amyloid-β(Aβ) aggregation is a major hallmark of Alzheimer's disease (AD). Previous studies have suggested that only unbound Aβ can take part in the aggregation process. Therefore, endogenous Aβ-binding proteins may have an important role in preventing AD. Here, we analyzed cerebrospinal fluid (CSF) samples from 35 subjects with AD, 18 subjects with frontotemporal dementia (FTD) and 29 non-demented controls to test if reduced Aβ-binding capacity in CSF is a specific feature of AD. A panel of known Aβ-binding CSF proteins, including β-trace/prostaglandin D2 synthase (β-trace), transthyretin (TTR), cystatin C (CysC) and α₁-antitrypsin (AAT), were quantified and related to diagnosis and CSF levels of Aβ_1–38, Aβ_1–40 and Aβ_1–42. AD patients displayed a mild reduction in the CSF levels of β-trace (p = 0.020), CysC (p = 0.017), AAT (p = 0.019) and TTR (p = 0.012) compared with controls. While the reductions in AAT and TTR were AD-specific, the levels of β-trace and CysC were also reduced in FTD. As expected, CSF Aβ_1–42 was reduced in AD compared with controls (p = 0.00005) and with FTD patients (p = 0.015). Positive correlations between Aβ_1–42 and β-trace, CysC and TTR, respectively, were seen only in the AD group, suggesting that deficient Aβ-binding capacity in CSF may contribute to the amyloidogenic process in AD.