title: Small cisterno-lumbar gradient of phosphorylated Tau protein in geriatric patients with suspected normal pressure hydrocephalus.
abstract: BACKGROUND
  The composition of the cerebrospinal fluid (CSF) is not homogeneous, and concentrations of proteins from different origins diverge among ventricular, cisternal and lumbar CSF fractions. Concentrations of blood-derived proteins increase and of brain-derived proteins decrease from ventricular to lumbar fractions. We studied whether the origin of the CSF portion analysed may affect results in CSF analysis for dementia.
  
  
  METHODS
  In 16 geriatric patients with suspected normal pressure hydrocephalus [age 82.5 (76/87) years; median (25th/75th percentile)] a lumbar spinal tap of 40 ml was performed. The CSF was sequentially collected in 8 fractions of 5 ml with the 1st fraction corresponding to lumbar CSF, the 8th to cisterna magna-near CSF. Fractions were analysed for total protein, albumin, Tau protein (Tau), phosphorylated Tau (pTau), Amyloid beta 1-42 (Aβ1-42), Amyloid beta 1-40 (Aβ1-40), and the Aβ1-42/Aβ1-40 ratio.
  
  
  RESULTS
  The concentrations of total protein and albumin increased from cisternal to lumbar fractions due to diffusion-related accumulation from blood to CSF with significantly higher concentrations in fraction 1 compared to fraction 8. The concentrations of Tau showed a non-significant trend towards decreased values in lumbar samples, and pTau was slightly, but significantly decreased in the lumbar fraction 1 [26.5 (22.5/35.0) pg/ml] compared to the cistern-near fraction 8 [27.0 (24.2/36.3) pg/ml] (p = 0.02, Wilcoxon signed rank test). Aβ1-42, Aβ1-40, and the Aβ1-42/Aβ1-40 ratio remained almost constant.
  
  
  CONCLUSIONS
  According to the flow-related diverging dynamics of blood-derived and brain-derived proteins in CSF, the concentrations of Tau and pTau tended to be lower in lumbar compared to cisternal CSF fractions after a spinal tap of 40 ml. The differences reached statistical significance for pTau only. The small differences will not affect clinical interpretation of markers of dementia in the vast majority of cases.
authors: Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany.|Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.
authors: Marija
authors: M
authors: Djukic
authors: Department of Neurology, University Medical Center Goettingen (UMG), Göttingen, Germany.|Department of Neurology, University Medical Centre Mainz, Mainz, Germany.
authors: Annette
authors: A
authors: Spreer
authors: Department of Neurology, University Medical Center Goettingen (UMG), Göttingen, Germany.
authors: Peter
authors: P
authors: Lange
authors: Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.
authors: Stephanie
authors: S
authors: Bunkowski
authors: Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Georg August University Göttingen, Göttingen, Germany.
authors: Jens
authors: J
authors: Wiltfang
authors: Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany. rnau@gwdg.de.|Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany. rnau@gwdg.de.
authors: Roland
authors: http://orcid.org/0000-0001-8316-995X
authors: R
authors: Nau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002946:Cisterna Magna; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid*; D008159:Lumbar Vertebrae; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D013129:Spinal Puncture; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Amyloid beta 1–40; Amyloid beta 1–42; Cerebrospinal fluid; Phosphorylated Tau protein; Tau protein