Ventricular and Lumbar Cerebrospinal Fluid Concentrations of Alzheimer's Disease Biomarkers in Patients with Normal Pressure Hydrocephalus and Posttraumatic Hydrocephalus

Article type: Research Article

Authors: Brandner, Sebastian^a | Thaler, Christian^a | Lelental, Natalia^b | Buchfelder, Michael^a | Kleindienst, Andrea^a | Maler, Juan Manuel^b | Kornhuber, Johannes^b | Lewczuk, Piotr^{b; *}

Affiliations: [a] Department of Neurosurgery, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany | [b] Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany

Correspondence: [*] Correspondence to: Dr. Piotr Lewczuk, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Schwabachanlage 6, 91054 Erlangen, Germany. Tel.: +49 9131 85 34324; Fax: +49 9131 85 34 238; E-mail: [email protected].

Abstract: Background:Little information is available on the rostro-caudal concentration gradient of Alzheimer’s disease (AD) biomarkers. Objective:We studied the concentrations of amyloid-β (Aβ) peptides 1-42 and 1-40 as well as the Tau and pTau proteins in simultaneously collected ventricular and lumbar cerebrospinal fluid (CSF) samples. Methods:The samples were simultaneously collected from the ventricle and the lumbar spinal canal in two groups of patients: 10 subjects being treated for normal pressure hydrocephalus (NPH) by the placement of a ventriculo-peritoneal shunt and 5 patients treated simultaneously with an external ventricular drain and a lumbar CSF drain due to posttraumatic hydrocephalus (PTH). Results:The ventricular-lumbar (V/L) concentration ratio for Aβ1-40 was 0.81 in NPH patients and 0.71 in PTH patients. The V/L-ratio for Aβ1-42 was 0.84 in NPH, reflecting significantly higher concentrations in lumbar CSF than in ventricular CSF, and 1.02 in PTH patients. The V/L-ratios for Tau and pTau differed significantly depending on the diagnostic group: the median V/L-ratio for Tau was 6.83 in NPH patients but only 0.97 in PTH patients. The median V/L-ratio for pTau was 2.36 in NPH patients and 0.91 in PTH patients. Conclusions:We conclude that the rostro-caudal concentration gradient for brain-derived proteins (Tau and pTau in this study) depends on the diagnosis and clinical status of the patient, which were largely neglected in the previously postulated models.

Keywords: Amyloid-β, biomarker, cerebrospinal fluid, rostro-caudal gradient, tau

DOI: 10.3233/JAD-132708

Journal: Journal of Alzheimer's Disease, vol. 41, no. 4, pp. 1057-1062, 2014