Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer’s disease
Open accessAbstract
INTRODUCTION: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). METHODS: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis. RESULTS: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume. DISCUSSION: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
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Blood measures of p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40 have been shown to change in preclinical AD and can discriminate this state from CU individuals with non-AD pathological changes.
“Indeed, blood measures of p-tau181, p-tau217, p-tau231, glial fibrillary acid protein (GFAP), neurofilament light (NfL) and Aβ42/40 have been shown to change in preclinical AD and can discriminate this state from CU individuals with non-AD pathological changes1,3,6–13.”
From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [11]
Section 3.3 (page unavailable) reports higher p-tau181, p-tau231 and GFAP in cognitively unimpaired Aβ+ adults than in Aβ− adults, but no significant difference in NfL. The Discussion (page unavailable) mentions prior findings for p-tau217 and Aβ42/40, but neither was assessed in this study. The comparator was defined by absence of brain amyloidosis, not by the presence of non-AD pathological changes. (LLM, conf=0.89)
Experimental — accuracy not yet measuredAlzheimer's disease is a neuronal cell disorder that generates progressive dysfunction of neurons due to abnormal deposition of amyloid beta and hyperphosphorylated tau proteins, genetic susceptibility, and increased oxidative stress.
“AD is a neuronal cell disorder that generates progressive dysfunction of neurons due to the abnormal deposition of amyloid β (Aβ) and hyperphosphorylated tau proteins, genetic susceptibility, and increased oxidative stress.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [8]
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- Authors
- Chatterjee, P., Pedrini, S., Ashton, N. J., Tegg, M., Goozee, K., Singh, A. K., Karikari, T. K., Simrén, J., Vanmechelen, E., Armstrong, N. J., Hone, E., Asih, P. R., Taddei, K., Doré, V., Villemagne, V. L., Sohrabi, H. R., Zetterberg, H., Masters, C. L., Blennow, K., & Martins, R. N.
- Affiliations
- Edith Cowan University (AU)
- King's College London (GB)
- Macquarie University (AU)
- University of Gothenburg (SE)
- Sahlgrenska University Hospital (SE)
- ADx NeuroSciences (BE)
- Curtin University (AU)
- Flinders University (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- University of Pittsburgh (US)
- The University of Melbourne (AU)
- Corresponding author
- Martins, Ralph N.
- ORCID
- Chatterjee, Pratishtha
- Pedrini, Steve
- Ashton, Nicholas J.
- Tegg, Michelle
- Goozee, Kathryn
- Singh, Abhay K.
- Karikari, Thomas K.
- Simrén, Joel
- Vanmechelen, Eugeen
- Armstrong, Nicola J.
- Hone, Eugene
- Asih, Prita R.
- Taddei, Kevin
- Doré, Vincent
- Villemagne, Victor L.
- Sohrabi, Hamid R.
- Zetterberg, Henrik
- Masters, Colin L.
- Blennow, Kaj
- Martins, Ralph N.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2021-09-08
- Volume
- 18
- Issue
- 6
- Pages
- 1141-1154
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W3196908729
- Cited by
- 231
- References
- 45
- Citations by year
- 2026: 35 · 2025: 52 · 2024: 59 · 2023: 52 · 2022: 31 · 2021: 2
- FWCI
- 25.81
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Murdoch University Research Portal (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Research Online (Edith Cowan University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Australian Alzheimer's Research Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- preclinical Alzheimer's disease, plasma biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Amyloidosis, Humans, Prognosis, Biomarkers, Amyloid beta-Peptides, tau Proteins
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