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Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease

Chatterjee, P; Pedrini, S; Stoops, E; Goozee, K; Villemagne, VL; Asih, PR; Verberk, IMW; ... Martins, RN; + view all (2021) Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease. Translational Psychiatry , 11 (1) , Article 27. 10.1038/s41398-020-01137-1. Green open access

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Abstract

Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer's disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1-42/Aβ1-40 ratio, a blood-based marker associated with brain Aβ load, in participants (65-90 years) categorised into low (Aβ-, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1-42, and Aβ1-40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1-42/Aβ1-40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ- participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ- (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1-42/Aβ1-40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1-42/Aβ1-40 ratios) for cognitively normal older adults at risk of AD.

Type: Article
Title: Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41398-020-01137-1
Publisher version: https://doi.org/10.1038/s41398-020-01137-1
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10119941
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