Plasma glial fibrillary acidic protein and neurofilament light chain are measures of disease severity in semantic variant primary progressive aphasia
Open accessAbstract
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. ### Participants 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. …
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Some studies reported elevated blood GFAP in participants with FTD compared to controls.
“Indeed, some studies reported elevated blood GFAP in participants with FTD compared to controls [8–18] but others observed no such GFAP increase in FTD [19–22].”
Other investigators did not find that blood GFAP concentrations correlate with clinical markers of disease severity in participants with FTD.
“Similarly, some investigators [8, 11, 14] but not others [9, 21–23] found that blood GFAP concentrations correlate with clinical markers of disease severity in participants with FTD.”
A medium to strong positive correlation between serum GFAP and serum NfL has been previously described in controls, FTD and AD.
“A medium to strong positive correlation between serum GFAP and serum NfL was observed in all diagnostic groups, and has been previously described in controls, FTD and AD [83, 84].”
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Cites
Classification of primary progressive aphasia and its variants
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Self-citationSerum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia
Rohrer, J. D., Woollacott, I., Dick, K. M., Brotherhood, E., Gordón, E., Fellows, A. D., Toombs, J., Druyeh, R., Cardoso, M. J., Sebastien Ourselin, A., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003154 · Cited by 431 · see citing works
Self-citationCardoso, M. J., Marc Modat, A., Wolz, R., Melbourne, A., Cash, D. M., Rueckert, D., & Sebastien Ourselin, A. (2015) · IEEE Transactions on Medical Imaging · doi:10.1109/tmi.2015.2418298 · Cited by 343 · see citing works
Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
Heller, C., Foiani, M. S., Moore, K., Convery, R., Bocchetta, M., Neason, M., Cash, D. M., Thomas, D., Greaves, C. V., Woollacott, I. O., et al. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-321954 · Cited by 182 · see citing works
Self-citationTDP-43 frontotemporal lobar degeneration and autoimmune disease
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Self-citationClinical value of cerebrospinal fluid neurofilament light chain in semantic dementia
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“Similarly, some investigators [8, 11, 14] but not others [9, 21–23] found that blood GFAP concentrations correlate with clinical markers of disease severity in participants with FTD. Small cohort sizes and the heterogeneity of FTD spectrum disorders may underlie these discrepancies.”
Influential
- Authors
- Heller, C., Chan, E., Foiani, M. S., Todd, E., Russell, L. L., Greaves, C. V., Heslegrave, A. J., Warren, J. D., Zetterberg, H., Bocchetta, M., & Rohrer, J. D.
- Affiliations
- UK Dementia Research Institute (GB)
- UCL Queen Square Institute of Neurology (GB)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Rohrer, Jonathan D
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2020-11-20
- Volume
- 92
- Issue
- 4
- Pages
- 455-456
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W3098120168
- Cited by
- 15
- References
- 7
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd (#2018-02532)
- Medical Research Council (MR/M008525/1, MR/M023664/1)
- Swedish State Support for Clinical Research (ALFGBG-720931)
- National Institute for Health Research (BRC149/NS/MH)
- Alzheimer Drug Discovery Foundation (201809-2016862)
- H2020 European Research Council (681712)
- EU Joint Programme - Neurodegenerative Disease Research (2019-02248)
- Alzheimer's Society (AS-JF-19a-004-517)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- semantic dementia, glial fibrillary acidic protein, neurofilament light chain, plasma biomarkers, disease severity, frontotemporal dementia, TDP-43 pathology, astroglial activation, neurodegeneration, semantic knowledge
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