Studying the natural history of frontotemporal lobar degeneration (FTLD): The ARTFL LEFFTDS longitudinal FTLD (ALLFTD) protocol
Authors: Boeve Bradley F. , Boxer Adam L. , Rosen Howard J. , Forsberg Leah K. , Heuer Hilary W. , Brushaber Danielle , Appleby Brian , Biernacka Joanna M. , Bordelon Yvette M. , Botha Hugo , Brannelly Patrick , Dickerson Brad C. , Dickson Dennis W. , Kimiko Domoto‐Reilly , Faber Kelley , Fagan Anne , Fields Julie A. , Fishman Ann , Foroud Tatiana M. , Galasko Doug R. , Gavrilova Ralitza H. , Gendron Tania F. , Geschwind Daniel H. , Ghoshal Nupur , Goldman Jill , Graff‐Radford Jonathan , Graff‐Radford Neill R. , Grant Ian , Grossman Murray , Hsiung Ging‐Yuek Robin , Huang Eric J. , Huey Edward , Irwin David J. , Jones David T. , Kantarci Kejal , Karydas Anna M. , Kaufer Daniel , Knopman David S. , Kramer Joel H. , Kremers Walter K. , Kornak John , Kukull Walter A. , Lagone Emma , Leger Gabriel C. , Litvan Irene , Ljubenkov Peter A. , Lucente Diane E , Mackenzie Ian R , Manoochehri Masood , Masdeu Joseph C. , McGinnis Scott , Mendez Mario F. , Miller Bruce L. , Miyagawa Toji , Nelson Kevin M. , Onyike Chiadi U , Pantelyat Alex , Pascual Belen , Pearlman Rodney , Petrucelli Leonard , Rademakers Rosa , Ramos Eliana Marisa , Rankin Katherine , Rascovsky Katya , Rexach Jessica E. , Ritter Aaron , Roberson Erik D. , Rojas Julio C. , Sabbagh Marwan N. , Salmon David P. , Savica Rodolfo , Seeley William W. , Staffaroni Adam M. , Syrjanen Jeremy , Tartaglia Carmela , Tatton Nadine , Taylor Joanne , Toga Arthur W. , Weintraub Sandra , Wheaton Diana , Wong Bonnie , Wszolek Zbigniew 
Published: December 2020

AbstractBackgroundIt is important to determine the natural history of sporadic and familial frontotemporal lobar degeneration (FTLD) and generate clinical, neuropsychological, neuroimaging and biofluid data for planning disease‐modifying trials.MethodAs part of the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD; U19 AG063911) protocol, investigators at 19 centers in North America will enroll 2100 participants with FTLD over the next 5 years beginning in early 2020.ResultAs of 1/20/20, the ARTFL/LEFFTDS (A/L) Consortium had enrolled 1832 participants, including 850 in kindreds with familial FTLD (239 associated with mutations in MAPT, 192 in GRN, 370 in C9orf72, 4 with mutations in both GRN and C9orf72, and 45 with a mutation in a different gene or no mutation in any known FTLD‐associated gene). Over 500 participants have undergone 2 or more annual visits to date. MRI has been performed in 1105. Biofluid samples have also been collected, with blood (DNA, plasma, serum, mRNA, PBMC) in 1413 and CSF in 303. Over 60 manuscripts using A/L data or samples have been published to date. Five clinical trials involving A/L and ALLFTD participants are in progress or planned. The longitudinal arm in ALLFTD will enroll 500 of existing A/L and 600 future participants for annual assessments with similar methodology to A/L. An additional 1000 FTLD patients will undergo focused one‐time clinical evaluations and biofluid collection.ConclusionThe data/samples from already‐enrolled and planned participants in ALLFTD and findings published to date underscore the utility of evaluating FTLD subjects. The absence of identifiable mutations in some with familial FTLD suggests that other genes are yet to be discovered. ALLFTD data will inform clinical trial design, and many participants will be eligible for future trials. The key data and samples in ALLFTD are available to interested investigators worldwide. Supported by: AG063911, AG045390, NS092089, AG016976, AG21886.