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Semantic variant primary progressive aphasia (svPPA) is a neurodegenerative disorder characterised by loss of conceptual knowledge, commonly presenting with word-finding difficulties, impaired single word comprehension and focal atrophy of the temporal lobe.1 It is a subtype of frontotemporal dementia (FTD) and usually associated with TDP-43 type C pathology. While much progress has been made in the last 20 years in understanding the cognitive and biological nature of svPPA, there have been limited studies of fluid biomarkers.2 In this study, we investigated the role of plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as biomarkers for astroglial activation and neurodegeneration in svPPA, as well as their association with disease severity in svPPA.
Plasma samples were collected from 64 consecutively recruited participants from the University College London FTD cohort studies: 28 participants meeting diagnostic criteria for svPPA1 and 36 healthy controls. There was no statistical difference in age or sex between the two groups (t-test, p=0.934 and Fisher’s exact test, p=1.000, respectively). Participants underwent a standardised clinical and cognitive assessment (table 1) including two measures of semantic knowledge, Wechsler Abbreviated Scale of Intelligence (WASI) Vocabulary subtest and the British Picture Vocabulary Scale (BPVS, a word-picture matching task). They also underwent a 3D T1-weighted MRI of the brain on either a Siemens Trio or Prisma 3T scanner with 55 scans passing initial quality control for cross-sectional analysis (21 participants with svPPA and 34 healthy controls): temporal lobe grey matter volumes (combined left and right hemisphere) were calculated using a previously described automated segmentation technique.3 4 The local ethics committee approved the study and all participants provided written informed consent at enrolment. …
Contributors CH, EC and JDR contributed to the study design, acquisition, analysis and interpretation of the data as well as drafting and revising the manuscript. MSF, ET, LLR, CVG, AJH, JDW, HZ and MB contributed to the acquisition of data and study coordination as well as helping to critically review and revise the manuscript.
Funding The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from 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). MB is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). 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 UK Dementia Research Institute at UCL, the Wellcome Trust and an anonymous donor.
Competing interests HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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