Reduced levels of amyloid-beta-binding proteins in cerebrospinal fluid from Alzheimer's disease patients.

• Amyloid-beta(Abeta) aggregation is a major hallmark of Alzheimer's disease (AD). Previous studies have suggested that only unbound Abeta can take part in the aggregation process. Therefore, endogenous Abeta-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 Abeta-binding capacity in CSF is a specific feature of AD. A panel of known Abeta-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 Abeta(1-38), Abeta(1-40) and Abeta(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 Abeta(1-42) was reduced in AD compared with controls (p=0.00005) and with FTD patients (p=0.015). Positive correlations between Abeta(1-42) and beta-trace, CysC and TTR, respectively, were seen only in the AD group, suggesting that deficient Abeta-binding capacity in CSF may contribute to the amyloidogenic process in AD.

Keyword

Aged

Aged

80 and over

Alzheimer Disease

cerebrospinal fluid

Amyloid beta-Protein

cerebrospinal fluid

Cystatin C

cerebrospinal fluid

Dementia

cerebrospinal fluid

Electrochemistry

Female

Humans

Intramolecular Oxidoreductases

cerebrospinal fluid

Linear Models

Lipocalins

cerebrospinal fluid

Male

Nephelometry and Turbidimetry

methods

Peptide Fragments

cerebrospinal fluid

Prealbumin

cerebrospinal fluid

Statistics

Nonparametric

alpha 1-Antitrypsin

cerebrospinal fluid

Publication and Content Type

ref (subject category)

art (subject category)