Diagnostic accuracy of research criteria for prodromal frontotemporal dementia

Background The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagno sis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impair ment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI‑FTD in a cohort of genetically confirmed FTD cases against healthy controls. Methods A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non‑carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment. Results The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001). Conclusions The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases – Project ID No 739510. AB was supported by the Airalzh-AGYR2020, by Fondazione Cariplo (grant n° 2021-1516), and by the Fondation pour la Recherche sur Alzheimer. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, the Netherlands Organisation for Scientific Research (NWO) grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland, and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926, and 2018-02754; the Swedish FTD Inititative-Schörling Foundation; Alzheimer Foundation; Brain Foundation; and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Welcome Trust (220258), the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400), and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme – Neurodegenerative Disease Research (JPND) and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C); the Olav Thon Foundation; the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 860197 (MIRIADE); the European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694); and the UK Dementia Research Institute at UCL. JL received funding for this work from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). 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)

Schinus terebinthifolius countercurrent chromatography (Part II): Intra-apparatus scale-up and inter-apparatus method transfer.

Countercurrent chromatography (CCC) is being widely used across the world for purification of various materials, especially in natural product research. The predictability of CCC scale-up has been successfully demonstrated using specially designed instruments of the same manufacturer. The reality is that the most of CCC users do not have access to such instruments and do not have enough experience to transfer methods from one CCC column to another. This unique study of three international teams is based on innovative approach to simplify the scale-up between different CCC machines using fractionation of Schinus terebinthifolius berries dichloromethane extract as a case study. The optimized separation methodology, recently developed by the authors (Part I), was repeatedly performed on CCC columns of different design available at most research laboratories across the world. Hexane - ethyl acetate - methanol - water (6:1:6:1, v/v/v/v) was used as solvent system with masticadienonic and 3β-masticadienolic acids as target compounds to monitor stationary phase retention and calculate peak resolution. It has been demonstrated that volumetric, linear and length scale-up transfer factors based on column characteristics can be directly applied to different i.d., volume and length columns independently on instrument make in an intra-apparatus scale-up and inter-apparatus method transfer.F.N. Costa and S. Ignatova would like to thank Newton AdvancedFellowship project funded by the Royal Society of the United King-dom, which made this international work feasible. M.N. Vieirathanks the Studienstiftung desdeutschen Volkes (Germany) for thePh.D. scholarship. The authors are indebted to Plantextrakt GmbH& Co. (Germany) for the supply of S. terebinthifolius berry material