Abstract Details

Title Characteristics and Progress on 369 Subjects in the Longitudinal Evaluation Familial Frontotemporal Dementia Subjects (LEFFTDS) Protocol

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-009

Objective

To report updated data from the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) protocol.

Background

The LEFFTDS Consortium (U01 AG045390) involves investigators at 8 centers in North America evaluating individuals in kindreds with mutations in microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes using a standardized battery of measures. Target enrollment was 300. Participants are evaluated at approximately yearly intervals.

Design/Methods

We report here the demographic, clinical and genetic characteristics of participants evaluated through 10/22/2018.

Results

There are 369 participants among approximately 65 kindreds enrolled to date who have undergone baseline (Visit 1) assessment with the following characteristics: 201 (55%) female, 344 (94%) Caucasian, mean age 49 (range 18-80) years, and mean education 15 (range 11-22) years. Using the FTLD-CDR, participants are classified as symptomatic (FTLD-CDR>0) or asymptomatic (FTLD-CDR=0). Characteristics for each genetic group are as follows: MAPT – with mutations IVS9-10G>T, IVS10+14C>T, IVS10+16C>T, N279K, P301L, S305I, S305N, V337M, G389R or R406W (32 FTLD-CDR>0, 90 FTLD-CDR=0); GRN – with mutations A9D, C31LfsX35, G35EfsX19, T52HfsX2, A89V, V90SfsX67, R110X, Q130SfsX125, R198GfsX19, S226WfsX28, A237WfsX4, V279GfsX5, Q300X, W304LfsX58, R418X, I422Efs, R493X and P512Lfs (29 FTLD-CDR>0, 67 FTLD-CDR=0); and C9orf72 – with the expansion (58 FTLD-CDR>0, 95 FTLD-CDR=0).. Two individuals have a double mutation – C9orf72 + GRN. Almost all participants have had volumetric MRI performed as well as DNA, plasma, RNA and PBMC samples collected. CSF has been collected in 47%. Annual follow-up evaluations have been completed in 258 (70%) for Visit 2, 134 (37%) for Visit 3, and 21 (6%) for Visit 4.

Conclusions

These clinical, neuropsychological and biomarker data, which are available to interested investigators worldwide, will facilitate planning for upcoming disease-modifying therapeutic trials in familial frontotemporal lobar degeneration.

Authors/Disclosures
Leah K. Forsberg, PhD (Mayo Clinic) PRESENTER	Ms. Forsberg has nothing to disclose.
	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.
Bradford Dickerson, MD, FAAN	Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lantheus. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Dickerson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Dickerson has received publishing royalties from a publication relating to health care. Dr. Dickerson has received publishing royalties from a publication relating to health care.
	No disclosure on file
Ralitza H. Gavrilova, MD (Mayo Clinic)	Dr. Gavrilova has nothing to disclose.
Nupur Ghoshal, MD, PhD (Washington University)	No disclosure on file
Jill S. Goldman, MS MPhil CGC (Columbia University Medical Center Taub Institute)	No disclosure on file
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville)	The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.
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
Ging-Yuek R. Hsiung, MD, FAAN (University of British Columbia)	Dr. Hsiung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Hsiung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Hsiung has received research support from CIHR. The institution of Dr. Hsiung has received research support from NIH. The institution of Dr. Hsiung has received research support from Eli Lilly. The institution of Dr. Hsiung has received research support from Biogen.
Edward Huey	No disclosure on file
David Irwin, MD (University of Pennsylvania)	The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.
Kejal Kantarci, MD (Mayo Clinic)	The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. The institution of Dr. Kantarci has received research support from Eisai. The institution of Dr. Kantarci has received research support from BioArctic.
Anna Karydas (UCSF)	No disclosure on file
David S. Knopman, MD, FAAN (Mayo Clinic)	Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
John Kornak	No disclosure on file
Walter Kremers	The institution of Walter Kremers has received research support from NIH. The institution of an immediate family member of Walter Kremers has received research support from NIH.
Walter Kremers	The institution of Walter Kremers has received research support from NIH. The institution of an immediate family member of Walter Kremers has received research support from NIH.
	No disclosure on file
	No disclosure on file
Ian R.A. Mackenzie, MD, FRCP (Vancouver General Hospital)	No disclosure on file
Rosa Rademakers, PhD (Mayo Clinic Dept of Neuroscience)	Rosa Rademakers, PhD has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mayo Clinic. Rosa Rademakers, PhD has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda Therapeutics. Rosa Rademakers, PhD 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 Alzheimer Fondation. Rosa Rademakers, PhD 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 Kisick Family Foundation (FTD grant program). The institution of Rosa Rademakers, PhD has received research support from NIH. The institution of Rosa Rademakers, PhD has received research support from DOD. The institution of Rosa Rademakers, PhD has received research support from Flanders Institute for Biotechnology (VIB). The institution of Rosa Rademakers, PhD has received research support from Flanders Funds for Scientific Research.
	No disclosure on file
	No disclosure on file
Arthur Toga (UCLA School of Medicine)	No disclosure on file
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville)	Dr. Wszolek 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 Polish Neurological Society/Via Medica. Dr. Wszolek has received intellectual property interests from a discovery or technology relating to health care.
Bradley F. Boeve, MD, FAAN (Mayo Clinic)	Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
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 received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. 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-5. Dr. Boxer has received research support from Rainwater Charitable Foundation. Dr. Boxer has received research support from GHR Foundation. Dr. Boxer has received intellectual property interests from a discovery or technology relating to health care.
Howard J. Rosen, MD (UCSF)	Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly . Dr. Rosen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alector. 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 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.

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