Cerebrospinal Fluid Soluble Amyloid-β Protein Precursor as a Potential Novel Biomarkers of Alzheimer's Disease

Article type: Research Article

Authors: Lewczuk, Piotr^{a; *; 1} | Popp, Julius^{b; c; *; 1} | Lelental, Natalia^a | Kölsch, Heike^c | Maier, Wolfgang^{c; d} | Kornhuber, Johannes^a | Jessen, Frank^{c; d}

Affiliations: [a] Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany | [b] Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland | [c] Department of Psychiatry, University of Bonn, Bonn, Germany | [d] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

Correspondence: [*] Correspondence to: Prof. Dr. med. Piotr Lewczuk, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany. Tel.: +49 9131 85 34324; Fax: +49 9131 85 34238; E-mail: Piotr.Lewczuk@uk-erlangen.de and Dr. med. Julius Popp, Department of Psychiatry, University Hospital of Lausanne, Rue du Mont, 1008 Prilly-Lausanne, Switzerland. Tel.: +41 21 314 82 60; Fax: +41 21 314 82 76; E-mail: Julius.Popp@chuv.ch.

Note: [1] Both authors contributed equally.

Abstract: In this report, we confirm our previous findings of increased concentrations of soluble amyloid-β protein precursor (sAβPP) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large cohort of patients (n = 314), not overlapping with those of our previous study, and we extend our observations by including a control group of participants with normal cognition. In addition, we investigate the effects of age, the APOEε4 genotype, and the blood-CSF barrier function on the concentrations of sAβPPα and sAβPPβ. The study participants were categorized according to clinical-neuropsychological criteria, supported by CSF neurochemical dementia diagnostics (NDD) analyses. sAβPPα concentrations in the AD group (132.0 ± 44.8) were significantly higher than in the control group (105.3 ± 37.3, p < 0.0005) but did not differ from the MCI-AD group (138.5 ± 39.5, p = 0.91). The MCI-AD group differed significantly from the MCI-O (97.3 ± 34.3, p < 0.05) group. There was no difference between the control and the MCI-O groups (p = 0.94). Similarly, sAβPPβ concentrations in the AD group (160.2 ± 54.3) were significantly higher than in the control group (129.9 ± 44.6, p < 0.005) but did not differ from the MCI-AD group (184.0 ± 56.4, p = 0.20). The MCI-AD group differed significantly from the MCI-O (127.8 ± 46.2, p < 0.05) group. There was no difference between the control and the MCI-O groups (p > 0.99). We observed highly significant correlation of the two sAβPP forms. Age and the CSF-serum albumin ratio were significant albeit weak predictors of the sAβPPα and sAβPPβ concentrations, while carrying the APOEε4 allele did not influenced the levels of the sAβPP forms. Taken together, the results strongly suggest that CSF sAβPP concentrations may be considered as an extension of already available NDD tools.

Keywords: Alzheimer's disease, amyloid-β protein precursor, biomarkers, cerebrospinal fluid

DOI: 10.3233/JAD-2011-110857

Journal: Journal of Alzheimer's Disease, vol. 28, no. 1, pp. 119-125, 2012