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

Background: Little information is available on the rostro-caudal concentration gradient of Alzheimer's disease (AD) biomarkers. Objective: We studied the concentrations of amyloid-beta (A beta) 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 A beta(1-40) was 0.81 in NPH patients and 0.71 in PTH patients. The V/L-ratio for A beta(1-42) 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.