Cellular signatures of functional resilience in presymptomatic frontotemporal dementia (2025)

Competing Interest Statement

All authors have no conflicts of interest. Untreated to this there are several disclosures.JBR is a non-remunerated trustee of the Guarantors of Brain, Darwin College, and the PSP Association; he provides consultancy to Alzheimer Research UK, Asceneuron, Alector, Biogen, CuraSen, CumulusNeuro, UCB, SV Health, and Wave, and has research grants from AZ-Medimmune, Janssen, Lilly as industry partners in the Dementias Platform UK.Prof. Lebouvier receives consultancy fees from Roche, Lilly, Biogen, and Eisai, which are directed entirely to his institution.M.M. has acted as a consultant for Astex Pharmaceuticals.

Funding Statement

K.A.T. was supported by Fellowship awards from the Guarantors of Brain (G101149) and the Alzheimer's Society, UK (Grant number 602).J.B.R was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312: BRC-1215-20014), NIHR funding to the NIHR BioResource (RG94028 & RG85445), Wellcome Trust (220258), Medical Research Council (SUAG/051G101400; SUAG/010 RG91365; MC_UU_00030/14 and MR/T033371/1), the Holt Fellowship and by the Addenbrookes Charitable Trust. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. The views expressed are those of the author(s) and not necessarily those of the NHS or the NIHR.J.C.V.S., L.C.J. and H.S. are supported by the Dioraphte Foundation grant 09-02-03-00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), ZonMw Onderzoeksprogramma Dementie (YOD-INCLUDED, project number10510032120002), EU Joint Programme-Neurodegenerative Disease Research-GENFI-PROX, Alzheimer Nederland and the Bluefield Project.C.G. received funding from EU Joint Programme-Neurodegenerative Disease Research-Prefrontals Vetenskapsrådet Dnr 529-2014-7504, EU Joint Programme-Neurodegenerative Disease Research-GENFI-PROX, Vetenskapsrådet 2019-0224, Vetenskapsrådet 2015-02926, Vetenskapsrådet 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation, Dementia Foundation and Region Stockholm ALF-project.C.G. is supported by the Swedish Frontotemporal Dementia Initiative Schörling Foundation; Vetenskapsrådet (Swedish Research Council) JPND Prefrontals, 2015-02926, 2018-02754, and JPND-GENFI-PROX 2019 02248; Swedish Alzheimer Foundation, ALF-project Region Stockholm, Karolinska Institutet Doctoral Funding, KI Strat-Neuro, Swedish Dementia Foundation, and Swedish Brain Foundation.D.G. received support from the EU Joint Programme Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042.R.V. has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia (Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie).J.L. received funding for this work by the Deutsche Forschungsgemeinschaft German Research Foundation under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy ID 390857198).E.F. has received funding from a Canadian Institute of Health Research grant #327387.MM was, in part, funded by the UK Medical Research Council, the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and also Canadian Institutes of Health Research operating grants (Grant #s: MOP-371851 and PJT-175242) and funding from the Weston Brain Institute to Mario Masellis.FM is supported by the Tau Consortium and has received funding from the Carlos III Health Institute (PI19/01637).Several authors of this publication (J.C.V.S., M.S., R.V., A.d.M., M.O., R.V., J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) – Project ID No 739510.This work was also supported by the EU Joint Programme-Neurodegenerative Disease Research GENFI-PROX grant [2019 02248; to J.D.R., M.O., B.B., C.G., J.C.V.S. and M.S.RS-V was funded at the Hospital Clinic de Barcelona by Instituto de Salud Carlos III, Spain (grant code PI20/00448 to RSV) and Fundaci ó Marat ó TV3, Spain (grant code 20143810 to RSV).RL is supported by the Canadian Institutes of Health Research and the Chaire de Recherche sur les Aphasies Primaires Progressives Fondation Famille Lemaire.This work was funded by Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie.SD receives salary funding from the Fonds de Recherche du Québec-Santé. This research was undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative.This work was supported by ANR-PRTS PREV-DemAls, PHRC PREDICT-PGRN and several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.This work was supported by the JPND grant “GENFI-prox” (by DLR/BMBF to M.S, joint with J.R., JvS, M.O., B.B. and C.G.).FM is supported by the Tau Consortium and has received funding from the Carlos III Health Institute (PI19/01637).BB is supported by JPND grant “GENFI-prox” (2019 02248).JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI PROX grant (2019 02248).For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was given a favorable opinion by the Cambridge 2 Research Ethics Committee REC 17/EE/0032 IRAS ID 204052.

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Yes

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