Abstract Details

Title A Comparative Study of Plasma t-tau and Neurofilament Light Chain in Frontotemporal Lobar Degeneration and Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S19 - Aging and Dementia (2:08 PM-2:16 PM)

Poster/Presentation
Number 002

Objective To compare the clinical value of total tau (t-tau) and neurofilament light chain (NfL) in frontotemporal lobar degeneration syndromes (FTLD-S), clinically-diagnosed Alzheimer’s dementia (AD-S) and pathology-proven cases.

Background Studies directly comparing the value of plasma t-tau and NfL in pathology-confirmed FTLD and AD are scarce.

Design/Methods We measured plasma t-tau and NfL with Simoa in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-Tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD). We compared cross-sectional and longitudinal biomarker concentrations between groups and their correlation with disease severity, progression, survival and cortical thickness.

Results NfL, but not t-tau, discriminated FTLD-S from HC [NfL ≥ 22.0 pg/mL, AUC .965 (.945–.986, p<.001, 100% specificity, 87.6% sensitivity) vs. t-tau ≥ 2.7 pg/mL, AUC .510 (.421–.598, p=.842, 78% specificity, 29% sensitivity)] and AD-S from HC [NfL ≥ 20.3 pg/mL, AUC .936 (.890–.986, p<.001, 95.6% specificity, 76.7% sensitivity) vs. t-tau ≥ 2.7 pg/mL, AUC .560 (.438–.685, p=.333, 78.2% specificity, 41.9% sensitivity)]. Both biomarkers were poor discriminators between FLTD-S and AD-S [NfL ≥ 38.6 pg/mL, AUC .748 (.677–.819, p<.001, 88.4% specificity, 76.7% sensitivity) vs. t-tau ≥ 3.7 pg/mL, AUC .578 (.484–.671, p=.115, 100% specificity, 7% sensitivity)]. In pathology-confirmed cases, NfL was higher in FTLD than AD (43.4 ± 28 pg/mL vs. 26.0 ± 20 pg/mL, p<.001) and in FTLD-TDP (85.6 ± 46 pg/mL) compared to FTLD-Tau (50.4 ± 26 pg/mL), after accounting for age and disease severity (p<.001; partial η²=.20). NfL, but not t-tau, predicted disease progression in both FTLD-S and AD-S and shorter survival in FLTD-S, and correlated with reduced cortical thickness in frontal regions in FLTD-S and temporoparietal regions in AD-S.

Conclusions Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.

Authors/Disclosures
Julio C. Rojas-Martinez, MD, PhD (UCSF) PRESENTER	Dr. Rojas-Martinez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ferrer International, S.A.. The institution of Dr. Rojas-Martinez has received research support from NIH/NIA. The institution of Dr. Rojas-Martinez has received research support from Eli Lilly. The institution of Dr. Rojas-Martinez has received research support from Eisai. The institution of Dr. Rojas-Martinez has received research support from Amylyx.
Ignacio Illan-Gala, Sr., MD, PhD (Hospital de la Santa Creu i Sant Pau)	Dr. Illan-Gala has nothing to disclose.
Alberto Lleo, MD (Hospital De La Santa Creu I Sant Pau)	Dr. Lleo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lleo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Lleo has received research support from Instituto de Salud Carlos III. The institution of Dr. Lleo has received research support from Generalitat de Calalunya (PERIS). The institution of Dr. Lleo has received research support from BBVA Foundation. The institution of Dr. Lleo has received research support from La Caixa Foundation. Dr. Lleo has received intellectual property interests from a discovery or technology relating to health care.
Adam Staffaroni	No disclosure on file
Henrik Zetterberg (Sahlgrenska University Hospital/Molndal)	Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley and Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.
	No disclosure on file
Lea Grinberg	Lea Grinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Inc. The institution of Lea Grinberg has received research support from NIH. The institution of Lea Grinberg has received research support from Eli Lilly. The institution of Lea Grinberg has received research support from BrightFouus. The institution of Lea Grinberg has received research support from Rainwater Charity Foundation.
Salvatore Spina, MD (UCSF Memory and Aging Center)	Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acsel Health. Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision Xtract. Dr. Spina has received research support from Tau Consortium. Dr. Spina has received research support from Chan Zuckerberg Initiative, LLC. Dr. Spina has received research support from Bluefield Project to Cure FTD.
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.
	No disclosure on file
Giovanni Coppola, MD (UCLA)	Dr. Coppola has received personal compensation for serving as an employee of Regeneron. Dr. Coppola has received stock or an ownership interest from Regeneron.
	No disclosure on file
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.
David Perry, MD	The institution of Dr. Perry has received research support from NIH/NIA.
Maria Luisa Gorno Tempini, MD, PhD (UCSF Memory and Aging Center)	The institution of Dr. Gorno Tempini has received research support from the NIH.
William W. Seeley, MD	Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG Council. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global Consulting. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BridgeBio. Dr. Seeley has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Seeley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lyterian Therapeutics. The institution of Dr. Seeley has received research support from NIH. The institution of Dr. Seeley has received research support from Rainwater Charitable Foundation. The institution of Dr. Seeley has received research support from Bluefield Project to Cure FTD. The institution of Dr. Seeley has received research support from Chan-Zuckerberg Initiative.
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.
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.

��ɫ��

��ɫ��