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

Article type: Research Article

Authors: Hansson, Sara F.^{a; *} | Andréasson, Ulf^a | Wall, Mariann^a | Skoog, Ingmar^b | Andreasen, Niels^c | Wallin, Anders^b | Zetterberg, Henrik^{a; d} | Blennow, Kaj^{a; d}

Affiliations: [a] Neurochemical Laboratory, Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital/Mölndal, Mölndal, Sweden | [b] Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Mölndal, Sweden | [c] Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden | [d] Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

Correspondence: [*] Corresponding author: Sara Hansson, Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital/Mölndal, S-431 80 Mölndal, Sweden. Tel.: +46 31 786 35 71; Fax: +46 31 34324 26; E-mail: sara.hansson@gu.se.

Note: [] Communicated by Sanna-Kaisa Herukka

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 Aβ1–38, Aβ1–40 and Aβ1–42. 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 Aβ1–42 was reduced in AD compared with controls (p = 0.00005) and with FTD patients (p = 0.015). Positive correlations between Aβ1–42 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.

Keywords: α₁-antitrypsin, Alzheimer's disease, amyloid-β, β-trace, cerebrospinal fluid, cystatin C, electrochemiluminescence, frontotemporal dementia, nephelometry, transthyretin

DOI: 10.3233/JAD-2009-0966

Journal: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 389-397, 2009