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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.
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1 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302)
2 Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302)
3 ADx NeuroSciences, Gent, Belgium (GRID:grid.1038.a)
4 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); KaRa Institute of Neurological Diseases, Macquarie Park, Australia (GRID:grid.489025.2); Anglicare, Castle Hill Sydney, Australia (GRID:grid.489025.2); University of Western Australia, School of Psychiatry and Clinical Neurosciences, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); The Cooperative Research Centre for Mental Health, Carlton South, Australia (GRID:grid.1012.2)
5 Austin Health, Department of Molecular Imaging & Therapy, Melbourne, Australia (GRID:grid.410678.c)
6 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405)
7 Amsterdam Neuroscience, Amsterdam University Medical Centers, Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam, Netherlands (GRID:grid.484519.5)
8 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Anglicare, Castle Hill Sydney, Australia (GRID:grid.1004.5)
9 Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); Australian Alzheimer’s Research Foundation, Nedlands, Australia (GRID:grid.429545.b) (ISNI:0000 0004 5905 2729)
10 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); Australian Alzheimer’s Research Foundation, Nedlands, Australia (GRID:grid.429545.b) (ISNI:0000 0004 5905 2729); School of Psychology and Exercise Science, College of Science, Health, Engineering and Education, Murdoch University, Centre for Healthy Ageing, Murdoch, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763)
11 University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X); UCL Institute of Neurology, Queen Square, Department of Neurodegenerative Disease, London, United Kingdom (GRID:grid.83440.3b) (ISNI:0000000121901201); UK Dementia Research Institute at UCL, London, UK (GRID:grid.83440.3b)
12 University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Mölndal, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)
13 Biomarkable, Gent, Belgium (GRID:grid.484519.5)
14 Macquarie University, Department of Biomedical Sciences, North Ryde, Australia (GRID:grid.1004.5) (ISNI:0000 0001 2158 5405); Edith Cowan University, School of Medical and Health Sciences, Joondalup, Australia (GRID:grid.1038.a) (ISNI:0000 0004 0389 4302); KaRa Institute of Neurological Diseases, Macquarie Park, Australia (GRID:grid.489025.2); University of Western Australia, School of Psychiatry and Clinical Neurosciences, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); The Cooperative Research Centre for Mental Health, Carlton South, Australia (GRID:grid.1012.2); Australian Alzheimer’s Research Foundation, Nedlands, Australia (GRID:grid.429545.b) (ISNI:0000 0004 5905 2729)