Cerebrospinal Fluid Alzheimer's Biomarkers and Neurofilament Light Profile of Idiopathic Normal Pressure Hydrocephalus in China: A PUMCH Cohort Study

Abstract

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is one of the potentially reversible dementias. Early and accurate diagnosis is important for patients' prognosis. Emerging evidence shows fluid biomarkers are useful in diagnosis and pathophysiological research of iNPH.

Methods: Probable iNPH and Alzheimer's disease (AD) patients were recruited. Clinical diagnosis was performed according to international guidelines. CSF collection complied with a standard protocol. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ42, and NfL.

Results: Twenty-seven iNPH, 27 AD, and 18 controls were included. The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and AD were significantly different (p < 0.0001). The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and control were not different (p > 0.05). Level of CSF Aβ42 in iNPH was significantly lower than control (p < 0.0001) and also significantly higher than AD (p < 0.05). NfL level in iNPH and AD was increased, but its level in iNPH was significantly lower than that in AD (p = 0.005). NfL and t-tau level in the iNPH group was significantly correlated (coefficient = 0.649, p = 0.005), but not in AD (coefficient = 0.298, p = 0.157).

Conclusion: Alzheimer's CSF biomarker profile of iNPH subjects showed moderately decreased Aβ42 and normal t-tau, p-tau181, and t-tau/Aβ42, which was distinguishable from AD. The different profiles and correlation of t-tau and NfL suggested different pathophysiology of AD and iNPH. t-tau was relatively an AD-specific neurodegenerative biomarker compared to NfL.

Keywords: Alzheimer’s disease; Biomarker; Cerebrospinal fluid; Idiopathic normal pressure hydrocephalus; Neurofilament light.