Abstract Details

Title Cerebrospinal Fluid Neurofilament Light as a Marker of Neuro-axonal Injury in Normal Pressure Hydrocephalus

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 7-001

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.

Authors/Disclosures
Foad Taghdiri, MD, MSc (University of Toronto) PRESENTER	Dr. Taghdiri has nothing to disclose.
	No disclosure on file
Anna Vasilevskaya, PhD	Anna Vasilevskaya has nothing to disclose.
Chloe Anastassiadis (Tanz Centre for Research on Neurodegenerative Disease)	Ms. Anastassiadis has received research support from Fonds de Recherche du Québec - Santé (FRQS).
Simrika Thapa, PhD (University Health Network)	Dr. Thapa has nothing to disclose.
Nico Paulo Dimal, MD	Dr. Dimal has nothing to disclose.
	No disclosure on file
Alfonso Fasano, MD, PhD, FAAN (Toronto Western Hospital - U of Toronto)	Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronic. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceregate. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Inbrain Neuroelectronics. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos Health. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annovis. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CADTH. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for International Parkinson and Movement Disorders Society. The institution of Dr. Fasano has received research support from Boston Scientific. The institution of Dr. Fasano has received research support from Medtronic. The institution of Dr. Fasano has received research support from Abbvie. The institution of Dr. Fasano has received research support from Canadian Institutes of Health Research (CIHR). The institution of Dr. Fasano has received research support from Michael J Fox Foundation. The institution of Dr. Fasano has received research support from Bluerock Therapeutics. Dr. Fasano has received publishing royalties from a publication relating to health care. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with CenteR for Advancing Neurological Innovation to Application (CRANIA) that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with HopeNET that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with International Essential Tremor Foundation that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Member with Tremor Research Group that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Co-Chair with Tremor Study Group of the IPMDS that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Vice-Chair with NPH Study Group of the IPMDS that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Vice-Chair with Industry Committee of the IPMDS that is relevant to AAN interests or activities.
David F. Tang-Wai, MD, FRCPC (Toronto Western Hospital/University Health Network)	Dr. Tang-Wai has nothing to disclose.
Carmela Tartaglia, MD (Toronto Western Hospital, University of Toronto)	Dr. Tartaglia has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Tartaglia has received research support from NIH. The institution of Dr. Tartaglia has received research support from University of Toronto.

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