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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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 <i>t</i>-tau, <i>p</i>-tau<sub>181</sub>, Aβ<sub>42</sub>, and NfL. <b><i>Results:</i></b> Twenty-seven iNPH, 27 AD, and 18 controls were included. The profiles of CSF <i>t</i>-tau, <i>p</i>-tau<sub>181</sub>, and <i>t</i>-tau/Aβ<sub>42</sub> in the iNPH and AD were significantly different (<i>p</i> < 0.0001). The profiles of CSF <i>t</i>-tau, <i>p</i>-tau<sub>181</sub>, and <i>t</i>-tau/Aβ<sub>42</sub> in the iNPH and control were not different (<i>p</i> > 0.05). Level of CSF Aβ<sub>42</sub> in iNPH was significantly lower than control (<i>p</i> < 0.0001) and also significantly higher than AD (<i>p</i> < 0.05). NfL level in iNPH and AD was increased, but its level in iNPH was significantly lower than that in AD (<i>p</i> = 0.005). NfL and <i>t</i>-tau level in the iNPH group was significantly correlated (coefficient = 0.649, <i>p</i> = 0.005), but not in AD (coefficient = 0.298, <i>p</i> = 0.157). <b><i>Conclusion:</i></b> Alzheimer’s CSF biomarker profile of iNPH subjects showed moderately decreased Aβ<sub>42</sub> and normal <i>t</i>-tau, <i>p</i>-tau<sub>181</sub>, and <i>t</i>-tau/Aβ<sub>42</sub>, which was distinguishable from AD. The different profiles and correlation of <i>t</i>-tau and NfL suggested different pathophysiology of AD and iNPH. <i>t</i>-tau was relatively an AD-specific neurodegenerative biomarker compared to NfL.

Comparison of cerebrospinal fluid space between probable normal pressure hydrocephalus and Alzheimer’s disease

“…With the VBM method, brain tissue scans are automatically segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The volumes of GM, WM, and CSF are then calculated separately and combined to obtain the total intracranial volume (TIV) ( Manniche et al, 2019 ; Mao et al, 2020 ). This is achieved by utilizing a prior probability map or “Bayesian prior,” which represents the spatial distribution of different tissue types in healthy individuals.…”