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

Amyloid-beta (A beta) aggregation is a major hallmark of Alzheimer's disease (AD). Previous studies have suggested that only unbound A beta can take part in the aggregation process. Therefore, endogenous A beta-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 A beta-binding capacity in CSF is a specific feature of AD. A panel of known A beta-binding CSF proteins, including beta-trace/prostaglandin D2 synthase (beta-trace), transthyretin (TTR), cystatin C (CysC) and alpha(1)-antitrypsin (AAT), were quantified and related to diagnosis and CSF levels of A beta(1-38), A beta(1-40) and A beta(1-42). AD patients displayed a mild reduction in the CSF levels of beta-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 beta-trace and CysC were also reduced in FTD. As expected, CSF A beta(1-42) was reduced in AD compared with controls (p = 0.00005) and with FTD patients (p = 0.015). Positive correlations between A beta(1-42) and beta-trace, CysC and TTR, respectively, were seen only in the AD group, suggesting that deficient A beta-binding capacity in CSF may contribute to the amyloidogenic process in AD.