Two‐point dynamic observation of Alzheimer’s disease cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

Abstract

AbstractBackgroundExtensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one‐point observation.ObjectiveTo investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients.MethodsWe analyzed CSF concentrations of tau, amyloid‐β (Aβ) 42 and 40, and leucine rich α‐2‐glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two‐point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo‐peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF).ResultsTau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aβ42 (LD/FD = 0.80, p < 0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p < 0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with LD concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively.ConclusionsDynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH. CSF circulation is disturbed in iNPH and old style one‐point CSF biomarker observation can be misestimated. This study detected dynamic changes of CSF biomarkers in iNPH during routine tap test and revealed the linkage between 1ml Last Drip of lumbar CSF and ventricular CSF.