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

Pratishtha Chatterjee, Steve Pedrini, Erik Stoops, Kathryn Goozee, Victor L. Villemagne, Prita R. Asih, Inge M.W. Verberk, Preeti Dave, Kevin Taddei, Hamid R. Sohrabi, Henrik Zetterberg, Kaj Blennow, Charlotte E. Teunissen, Hugo M. Vanderstichele, Ralph N. Martins*

*Corresponding author for this work

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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.

    Original languageEnglish
    Article number27
    Pages (from-to)1-10
    Number of pages10
    JournalTranslational Psychiatry
    Volume11
    Issue number1
    DOIs
    Publication statusPublished - 11 Jan 2021

    Bibliographical note

    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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