Characteristics and Progress on 312 Subjects in the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Protocol (P3.036)

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 is 300. Participants are reevaluated at approximately yearly intervals. Design/Methods: We report here the demographic, clinical and genetic characteristics of participants evaluated through September 30, 2017. Results: There are 312 participants among 65 kindreds enrolled to date for baseline (Visit 1) assessment with the following characteristics: 169 (54%) female, 299 (96%) Caucasian, mean age 50 (range 18–80) years, and mean education 15 (range 11–20) years. Using a modified version of the CDR, subjects are classified as symptomatic (CDRu003e0) or asymptomatic (CDR=0). Characteristics for each genetic group are as follows: MAPT – 18 kindreds with mutations −10, +14, +16, N279K, P301L, S305I, S305N, V337M, G389R or R406W; 100 participants (31 CDRu003e0, 69 CDR=0); GRN – 20 kindreds with mutations - A9D, C31LfsX35, T52HfsX2, A89V, V90SfsX67, R110X, Q130SfsX125, R198GfsX19, S226WfsX28, A237WfsX4, V279GfsX5, Q300X, W304LfsX58, R418X, I422Efs (novel), R493X and P512Lfs (novel); 85 participants (24 CDRu003e0, 61 CDR=0); and C9orf72 – 27 kindreds with the expansion; 104 participants (38 CDRu003e0, 66 CDR=0); and 23 yet to be characterized. 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 44%. Annual follow-up evaluations have been completed in 117 (57%) for Visit 2 and 25 (8%) for Visit 3. Conclusions: These clinical, neuropsychological and biomarker data, which are available to interested investigators worldwide, should facilitate planning for upcoming disease-modifying therapeutic trials in familial frontotemporal lobar degeneration. Study Supported by: U01 AG045390 and U54 NS092089 Disclosure: Dr. Boeve has received research support from GE Heathcare and Axovant. Dr. Rosen has nothing to disclose. Dr. Boxer has nothing to disclose. Dr. Brushaber has nothing to disclose. Dr. Coppola has nothing to disclose. Dr. Dheel has nothing to disclose. Dr. Dickerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Lilly, Biogen, Piramal. Dr. Faber has nothing to disclose. Dr. Fields has nothing to disclose. Dr. Fong has nothing to disclose. Dr. Foroud has nothing to disclose. Dr. Gavrilova has nothing to disclose. Dr. Ghoshal has nothing to disclose. Dr. Goldman has nothing to disclose. Dr Graff-Radford has nothing to disclose. Dr. Graff-Radford has nothing to disclose. Dr. Grossman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GE Whitney. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. Heuer has nothing to disclose. Dr. Hsiao has nothing to disclose. Dr. Hsiung has nothing to disclose. Dr. Huey has nothing to disclose. Dr Irwin has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Kantarci has nothing to disclose. Dr. Karydas has nothing to disclose. Dr. Knopman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Pharmaceuticals and the DIAN study. Dr. Kornak has nothing to disclose. Dr. Kramer has nothing to disclose. Dr. Kukull has nothing to disclose. Dr. Lapid has nothing to disclose. Dr. Mackenzie has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Petrucelli has nothing to disclose. Dr. Potter has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Rankin has nothing to disclose. Dr. Sutherland has nothing to disclose. Dr. Syrjanen has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Toga has nothing to disclose. Dr. Weintraub has nothing to disclose. Dr. Wszolek has received personal compensation in an editorial capacity for Elsevier - Parkinsonism u0026 Related Disorders, and Wiley - European Journal of Neurology. Dr. Wszolek has received royalty, license fees, or contractual rights payments from Mayo Clinic and I have a financial interest in technologies entitled, “Identification of Mutations in PARK8, a Locus for Familial Parkinson’s Disease” and “Identification of a Novel LRRK2 Mutation, 6055Gu003eA (G2019S), Linked to Autosomal Dominant Par.