Neprilysin-Like Activity Correlates with CSF-Tau and Phospho-Tau in Patients with Alzheimer's Disease

Article type: Research Article

Authors: Sorensen, Katrine Christa Nordskov^a | Simonsen, Anja Hviid^b | Holmetoft, Ulla Bachmann^a | Hasselbalch, Steen Gregers^b | Heegaard, Niels H.H.^{a; *}

Affiliations: [a] Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark | [b] Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Correspondence: [*] Correspondence to: Niels H. H. Heegaard, Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark. Tel.: +45 3268 3378; Fax: +45 3268 8265; E-mail: nhe@ssi.dk.

Abstract: A relation between amyloid-β peptide (Aβ) accumulation and neprilysin (NEP), an Aβ degrading enzyme, has been proposed but studies of NEP and the levels of the pathological hallmarks of Alzheimer's disease (AD), Aβ and tau, in cerebrospinal fluid (CSF) are scarce. In this study, we measured the level and enzyme activity of NEP in serum and CSF, using a sandwich enzyme-linked immunosorbent assay and a fluorescence resonance energy transfer assay, respectively, in patients with AD, frontotemporal dementia (FTD), Creutzfeldt-Jakob disease (CJD), and depression. Results were correlated with the levels of CSF AD biomarkers Aβ42, hyperphosphorylated tau (p-tau), and total tau (t-tau). In serum, we found no differences in NEP-like activity or concentration between the groups and there were no correlations between NEP and AD biomarkers. In CSF, no influence of age or gender on NEP levels or enzyme activity was seen. However, NEP concentration was lower and the specific activity was higher in FTD compared to AD. Aβ42 levels in CSF did not correlate with NEP concentration or activity in the AD, CJD, or depression groups, but NEP-like activity and Aβ42 levels correlated significantly in the FTD group. In AD and depression, the NEP-like activity in CSF correlated with levels of p-tau, and, in the AD group, it also was correlated with t-tau levels. Our results suggest that the relation between the specific activity of NEP and t-tau and p-tau is a characteristic trait of AD. The correlation between NEP concentration and Aβ42 in FTD is unexpected and warrants further investigation.

Keywords: Alzheimer's disease, amyloid-β₄₂, cerebrospinal fluid, depression, frontotemporal dementia, hyperphosphorylated tau, neprilysin, serum, total tau

DOI: 10.3233/JAD-122410

Journal: Journal of Alzheimer's Disease, vol. 37, no. 2, pp. 379-387, 2013