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.
Hansson
Sara F
SF
Neurochemical Laboratory, Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital/Mölndal, Mölndal, Sweden. sara.hansson@gu.se
Andréasson
Ulf
U
Wall
Mariann
M
Skoog
Ingmar
I
Andreasen
Niels
N
Wallin
Anders
A
Zetterberg
Henrik
H
Blennow
Kaj
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D055316:Cystatin C / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid; D004563:Electrochemistry; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid; D016014:Linear Models; D054834:Lipocalins / Q000134:cerebrospinal fluid; D008297:Male; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011228:Prealbumin / Q000134:cerebrospinal fluid*; D018709:Statistics, Nonparametric; D000515:alpha 1-Antitrypsin / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D055316:Cystatin C; D054834:Lipocalins; D010446:Peptide Fragments; D011228:Prealbumin; D000515:alpha 1-Antitrypsin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase