Abstract Details

Title Increased CSF Neurofilament Light Chain Reflects Disease Severity in Frontotemporal Degeneration

Topic Aging and Dementia

Presentation(s) S34 - (-)

Poster/Presentation
Number 005

Objective

Background CSF NfL is thought to be a marker of axonal damage that is elevated in a variety of neurological disorders including FTD. The clinical correlates of CSF NfL in FTD have not been determined.

Design/Methods We conducted a cross-sectional comparison of CSF from 30 normal controls, 40 FTD (16bvFTD, 7 progressive non-fluent aphasia [PNFA], 8 semantic dementia [SD]), 12 progressive supranuclear palsy (PSP), 32 Alzheimer's disease (AD) and 30 normal controls (NC). CSF was analyzed by: 1) INNO-BIA AlzBio3 immunosassay for Tau, pTau and A?42 and 2) ELISA for NfL. Genetic/PiB characterized cases were also considered. Voxel-based morphometry (VBM) of MRI images was used to confirm volumetric differences between FTD and controls, as well as the relationship between grey matter volume and NfL levels in FTD.

Results AD had lower A?42 readings compared to all groups (p<0.001). Both FTD and AD displayed higher tau and ptau levels, than PSP (p<0.028) and healthy controls (p<0.002). bvFTD and SD had higher NfL than AD (p<0.017) and PSP (p<0.013), with bvFTD also higher than NC (p=0.003). NfL was positively correlated with disease severity in FTD as measured by CDR-SB (p=0.004). These findings were confirmed in the subset of genetic/PIB(-) FTD patients. Using VBM, there was a negative correlation between left medial frontal gyrus volume and CSF NfL in FTD (p=0.0004), with higher NfL corresponding to more atrophy.

Conclusions NfL levels are elevated in bvFTD and SD as compared to AD, PSP and NC. Since CSF NfL is correlated with disease severity and brain atrophy in FTD-specific brain regions, this measurement may potentially be useful as a surrogate endpoint in FTD clinical trials. Studies of NfL in longitudinal FTD CSF samples are warranted.

Authors/Disclosures
Carole S. Scherling, PhD (UCSF, Memory & Aging Center) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Anna Karydas (UCSF)	No disclosure on file
	No disclosure on file
Joel Kramer, PhD (UCSF Medical Center)	The institution of Dr. Kramer has received research support from tau consortium. Dr. Kramer has received publishing royalties from a publication relating to health care.
Gil D. Rabinovici, MD, FAAN (UCSF Memory & Aging Center)	Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Norodisk. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for C2N. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Peerview. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer's Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with ANA.
	No disclosure on file
Mike Ahlijanian	No disclosure on file
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.
Howard J. Rosen, MD (UCSF)	Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharmaceuticals. Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Rosen has received research support from NIH. The institution of Dr. Rosen has received research support from State of CA. Dr. Rosen has a non-compensated relationship as a Consultant with Alector that is relevant to AAN interests or activities. Dr. Rosen has a non-compensated relationship as a Consultant with Prevail Therapeutics that is relevant to AAN interests or activities. Dr. Rosen has a non-compensated relationship as a consultant with Alchemab that is relevant to AAN interests or activities.
	No disclosure on file
Adam L. Boxer, MD, PhD (University of California, San Francisco)	An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project. Dr. Boxer has received research support from Rainwater Charitable Foundation.

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