Temporal order of clinical and biomarker changes in familial frontotemporal dementia.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
11
12
2021
accepted:
08
07
2022
pubmed:
23
9
2022
medline:
15
10
2022
entrez:
22
9
2022
Statut:
ppublish
Résumé
Unlike familial Alzheimer's disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes and plasma neurofilament light chain (NfL) in 796 carriers and 412 noncarrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations using model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. f-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects.
Identifiants
pubmed: 36138153
doi: 10.1038/s41591-022-01942-9
pii: 10.1038/s41591-022-01942-9
pmc: PMC9951811
mid: NIHMS1830996
doi:
Substances chimiques
Biomarkers
0
C9orf72 Protein
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2194-2206Subventions
Organisme : NIA NIH HHS
ID : K23 AG061253
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058233
Pays : United States
Organisme : NIA NIH HHS
ID : K24 AG045333
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG072122
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032306
Pays : United States
Organisme : Department of Health
ID : BRC149/NS/MH
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K010395/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : U54 NS092089
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG073514
Pays : United States
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : L30 AG069301
Pays : United States
Organisme : Medical Research Council
ID : SUAG/092 G116768
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : Medical Research Council
ID : MR/M008525/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : RF1 AG029577
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG029577
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG038791
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063911
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD001459
Pays : United States
Organisme : Medical Research Council
ID : MR/M023664/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG066509
Pays : United States
Organisme : Medical Research Council
ID : MR/T046015/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : K23 AG059888
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072977
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062677
Pays : United States
Organisme : Wellcome Trust
ID : 220258
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG045390
Pays : United States
Investigateurs
Liana Apostolova
(L)
Sami Barmada
(S)
Bradley Boeve
(B)
Adam L Boxer
(AL)
Andrea Bozoki
(A)
David Clark
(D)
Giovanni Coppola
(G)
Ryan Darby
(R)
Dennis Dickson
(D)
Kelley Faber
(K)
Anne Fagan
(A)
Douglas R Galasko
(DR)
Ian M Grant
(IM)
Eric Huang
(E)
Diana Kerwin
(D)
Maria Lapid
(M)
Suzee Lee
(S)
Gabriel Leger
(G)
Joseph C Masdeux
(JC)
Scott McGinnis
(S)
Mario Mendez
(M)
Chiadi Onyike
(C)
M Belen Pascual
(MB)
Peter Pressman
(P)
Rosa Rademakers
(R)
Vijay Ramanan
(V)
Aaron Ritter
(A)
William W Seeley
(WW)
Jeremy Syrjanen
(J)
Jack C Taylor
(JC)
Sandra Weintraub
(S)
Aitana Sogorb Esteve
(AS)
Annabel Nelson
(A)
Caroline V Greaves
(CV)
David L Thomas
(DL)
Hanya Benotmane
(H)
Henrik Zetterberg
(H)
Jennifer Nicholas
(J)
Kiran Samra
(K)
Rachelle Shafei
(R)
Carolyn Timberlake
(C)
Thomas Cope
(T)
Timothy Rittman
(T)
Alberto Benussi
(A)
Enrico Premi
(E)
Roberto Gasparotti
(R)
Silvana Archetti
(S)
Stefano Gazzina
(S)
Valentina Cantoni
(V)
Andrea Arighi
(A)
Chiara Fenoglio
(C)
Elio Scarpini
(E)
Giorgio Fumagalli
(G)
Vittoria Borracci
(V)
Giacomina Rossi
(G)
Giorgio Giaccone
(G)
Giuseppe Di Fede
(G)
Paola Caroppo
(P)
Sara Prioni
(S)
Veronica Redaelli
(V)
David Tang-Wai
(D)
Ekaterina Rogaeva
(E)
Miguel Castelo-Branco
(M)
Morris Freedman
(M)
Ron Keren
(R)
Sandra Black
(S)
Sara Mitchell
(S)
Christen Shoesmith
(C)
Robart Bartha
(R)
Jackie Poos
(J)
Janne M Papma
(JM)
Lucia Giannini
(L)
Rick van Minkelen
(R)
Yolande Pijnenburg
(Y)
Benedetta Nacmias
(B)
Camilla Ferrari
(C)
Cristina Polito
(C)
Gemma Lombardi
(G)
Valentina Bessi
(V)
Michele Veldsman
(M)
Christin Andersson
(C)
Hakan Thonberg
(H)
Linn Öijerstedt
(L)
Vesna Jelic
(V)
Paul Thompson
(P)
Albert Lladó
(A)
Anna Antonell
(A)
Jaume Olives
(J)
Mircea Balasa
(M)
Nuria Bargalló
(N)
Sergi Borrego-Ecija
(S)
Ana Verdelho
(A)
Carolina Maruta
(C)
Catarina B Ferreira
(CB)
Gabriel Miltenberger
(G)
Frederico Simões do Couto
(F)
Alazne Gabilondo
(A)
Ana Gorostidi
(A)
Jorge Villanua
(J)
Marta Cañada
(M)
Mikel Tainta
(M)
Miren Zulaica
(M)
Myriam Barandiaran
(M)
Patricia Alves
(P)
Benjamin Bender
(B)
Carlo Wilke
(C)
Lisa Graf
(L)
Annick Vogels
(A)
Mathieu Vandenbulcke
(M)
Philip Van Damme
(P)
Rose Bruffaerts
(R)
Koen Poesen
(K)
Pedro Rosa-Neto
(P)
Serge Gauthier
(S)
Agnès Camuzat
(A)
Alexis Brice
(A)
Anne Bertrand
(A)
Aurélie Funkiewiez
(A)
Daisy Rinaldi
(D)
Dario Saracino
(D)
Olivier Colliot
(O)
Sabrina Sayah
(S)
Catharina Prix
(C)
Elisabeth Wlasich
(E)
Olivia Wagemann
(O)
Sandra Loosli
(S)
Sonja Schönecker
(S)
Tobias Hoegen
(T)
Jolina Lombardi
(J)
Sarah Anderl-Straub
(S)
Adeline Rollin
(A)
Gregory Kuchcinski
(G)
Maxime Bertoux
(M)
Thibaud Lebouvier
(T)
Vincent Deramecourt
(V)
Beatriz Santiago
(B)
Diana Duro
(D)
Maria João Leitão
(MJ)
Maria Rosario Almeida
(MR)
Miguel Tábuas-Pereira
(M)
Sónia Afonso
(S)
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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