LONGITUDINAL COMPARISON OF CSF BIOMARKERS OF NEURODEGENERATION IN PATIENTS WITH PROBABLE IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS (INPH)

Total and phosphorylated tau (T-tau, P-T181-tau) in CSF are considered biomarkers of neurodegeneration and disease progression in Alzheimer's disease (AD). Cytoskeletal protein neurofilament light (NFL) would be a universal biomarker of neurodegeneration. Pre-synaptic protein neurogranin (Ng) seems to measure early synaptic degeneration. Our objective was to evaluate biomarker stability prospectively after CSF shunt surgery in iNPH and compare lumbar (L-) and ventricular (V-) CSF. CSF was collected prior to CSF shunt by lumbar puncture. In addition, simultaneous lumbar (L-CSF) and shunt valve puncture (V-CSF) at 0 (1-73 months after CSF shunt placement), 3, 6 and 18 months in 39 patients shunted due to iNPH (26 with confirmed amyloid-β (Aβ) plaques and 13 patients without Aβ pathology in right frontal cortical brain biopsy) at the KUH in Finland. CSF samples were analyzed with commercial ELISAs. Absolute levels of all four biomarkers correlated highly between V-CSF and L-CSF (T-tau: R = 0.83, P-T181-tau: R = 0.92, NFL: R = 0.94, Ng: R = 0.9; all P < 0.0001) but were systematically lower in V-CSF (T-tau: 22%, P-tau: 20%, NFL: 32%, Ng: 21%). No significant difference was seen in the levels of T-tau, P-T181-tau and Ng over 18 months either in L-CSF or V-CSF. However, the NFL levels showed an overall decrease of 6% per month. The levels of measured biomarkers were 20-30% lower in intraventricular CSF compared with lumbar. Longitudinal follow up of 18 months shows that after initial upregulation post-surgery, T-tau, P-tau and Ng are stable in iNPH patients irrespective of the brain biopsy Aβ pathology, while NFL normalized towards its pre-shunt levels.