Cerebrospinal Fluid Neurofilament Light as a Marker of Neuro-axonal Injury in Normal Pressure Hydrocephalus
Carly Davenport1, Foad Taghdiri2, Anna Vasilevskaya1, Chloe Anastassiadis1, Simrika Thapa1, Nico Paulo Dimal3, Namita Multani1, Alfonso Fasano4, David Tang-Wai3, Carmela Tartaglia3
1Tanz Centre for Research on Neurogegenerative Disease, University of Toronto, 2University of Toronto, 3UHN Memory Clinic, 4Movement Disorders Centre, Toronto Western Hospital, University of Toronto
Objective:
To compare Cerebrospinal fluid (CSF) Neurofilament-light chain (NfL) and NfL/amyloid beta42 (Abeta42) ratio levels in normal pressure hydrocephalus (NPH) patients with healthy controls (HC), Alzheimer’s disease (AD), and Frontotemporal lobar degeneration (FTLD).
Background:
Levels of CSF NfL have been shown to be a marker of neuro-axonal injury and are elevated in neurodegenerative disease. One putative etiology of NPH involves axonal injury; however, low CSF Abeta42 has been reported in NPH. To control for the higher volume of CSF in NPH, the NfL/Abeta42 ratio was used.
Design/Methods:
120 patients with CSF analysis: (a) 46 NPH: ventriculomegaly on MRI or CT, negative AD biomarkers, clinical symptoms of NPH, improvement in gait after tap test; (b) 39 FTLD: 5 behavioural-variant frontotemporal dementia, 14 corticobasal syndrome, 4 frontotemporal dementia with motor neuron disease, 12 progressive supranuclear palsy, 2 semantic-variant primary progressive aphasia (PPA), and 2 non-fluent PPA; (c) 29 AD; and (d) 6 HC. Levels of CSF NfL were measured using single molecule array (Simoa) technology while Abeta42 was measured using a sandwich ELISA method (Innotest). All statistical analyses were corrected for multiple comparisons and age.
Results:
Log transformed NfL levels in the NPH group were significantly higher than HC (p < 0.05), but lower than FTLD and AD group (p <0 .001). Log transformed CSF NfL/Abeta42 ratio was significantly higher in the NPH group compared to HC (p<0.05); but no significant difference with FTLD and AD groups.
Conclusions:
Intermediate CSF NfL levels in NPH patients suggest that there is some neuro-axonal injury present - although less than in FTLD and AD. Further investigations are warranted to determine whether the NfL normalizes after shunting or the neuroaxonal injury is irreversible. NfL in NPH may help elucidate the pathophysiology of the disease.