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Abstract Details

Novel CSF biomarkers for frontotemporal lobar degeneration with lesions immunoreactive to TDP-43 (FTLD-TDP)
Aging and Dementia
(-)
001
There is currently no reliable way to predict the underlying FTLD pathology while the patients are still living, and an ante-mortem biomarker for one of the main FTLD subtypes (FTLD-TDP or FTLD-Tau) can significantly enhance the pathology-based FTLD diagnosis and clinical trials for FTLD-TDP and FTLD-Tau.
Two independent cohorts of patients with frontotemporal dementia (FTD) were recruited independently from Emory University (Atlanta, GA) and University of Pennsylvania (Penn; Philadelphia, PA) to undergo CSF analysis. These include patients with high likelihood FTLD-TDP (FTD patients with amyotrophic lateral sclerosis or FTD patients with mutations in PGRN or C9ORF72) and patients with high likelihood FTLD-Tau (FTD patients with progressive supranuclear palsy or FTD patients with mutations in MAPT). Levels of five CSF previously identified proteins were measured, along with levels of total Tau (t-Tau) and Tau phosphorylated at threonine 181 (p-Tau181).
29 Emory patients and 40 Penn patients participated in the study, including 43 patients with high likelihood FTLD-TDP and 26 patients with high likelihood FTLD-Tau. Using the Emory cohort, we validated the group level differences in CSF eotaxin-3, Fas, and IL-23 (p < 0.01) previously identified using the Penn cohort. We also identified the ratio of p-Tau181 to t-Tau (p/t-Tau ratio) to be significantly lower in Emory FTLD-TDP cases compared to Emory FTLD-Tau and AD cases. Using the Penn cohort as a validation set, p/t-Tau ratio alone is sufficient to identify FTLD-TDP with 88% sensitivity and 73% specificity.
CSF biomarkers have the potential of accurately identifying FTLD-TDP, and further development of this and other FTLD-TDP biomarkers will significantly accelerate the ante-mortem prediction of FTLD-TDP pathology and design of substrate-specific FTLD clinical trials.
Authors/Disclosures
William T. Hu, MD, PhD, FAAN (Rutgers Biomedical and Health Sciences) Dr. Hu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fujirebio. Dr. Hu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Beckman Coulter. Dr. Hu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apellis Pharmaceuticals. The institution of Dr. Hu has received research support from NIA. The institution of Dr. Hu has received research support from TMCity Foundation. The institution of Dr. Hu has received research support from Atlanta Family Foundation. The institution of Dr. Hu has received research support from Fujirebio Diagnostics.
No disclosure on file
Murray Grossman, MD, FAAN (University of Pennsylvania) Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
No disclosure on file
James J. Lah, MD, PhD (Emory Brain Health Center) Dr. Lah has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Diagnostics. The institution of Dr. Lah has received research support from Roche.
Christopher Giza, MD, FAAN (UCLA, Depts of Pediatrics and Neurosurgery) Dr. Giza has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medical Network Speakers Bureau. Dr. Giza has stock in Highmark Interactive. The institution of Dr. Giza has received research support from UCLA: Brain Injury Research Center, Steve Tisch BrainSPORT Program, Easton Clinic for Brain Health. Dr. Giza has received publishing royalties from a publication relating to health care. Dr. Giza has a non-compensated relationship as a Advisory Board with Major League Soccer that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Advisory Board with National Basketball Association that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Consultant with United States Soccer Federation that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Co-founder & Advisor with Symptomwise that is relevant to AAN interests or activities.
John Q. Trojanowski, MD, PhD (University of PA School of Med) Dr. Trojanowski has nothing to disclose.
Allan I. Levey, MD, PhD (Dept of Neurology Emory University) Dr. Levey has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genuv. Dr. Levey has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cognito Therapeutics. Dr. Levey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Levey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Karuna Pharmaceuticals. Dr. Levey has received stock or an ownership interest from NextSense. The institution of Dr. Levey has received research support from NIH. The institution of Dr. Levey has received research support from Biogen. The institution of Dr. Levey has received research support from Esai. The institution of Dr. Levey has received research support from AAN. The institution of Dr. Levey has received research support from State of Georgia. The institution of Dr. Levey has received research support from Novartis. The institution of Dr. Levey has received research support from Genentech. Dr. Levey has received intellectual property interests from a discovery or technology relating to health care. Dr. Levey has received personal compensation in the range of $500-$4,999 for serving as a NAPA Avisory Committee Co-Chair with US Dept of Health and Human Services.