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Title: | Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease. | Austin Authors: | Chatterjee, Pratishtha;Pedrini, Steve;Stoops, Erik;Goozee, Kathryn;Villemagne, Victor L ;Asih, Prita R;Verberk, Inge M W;Dave, Preeti;Taddei, Kevin;Sohrabi, Hamid R;Zetterberg, Henrik;Blennow, Kaj;Teunissen, Charlotte E;Vanderstichele, Hugo M;Martins, Ralph N | Affiliation: | Centre for Healthy Ageing, School of Psychology and Exercise Science, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom UK Dementia Research Institute at UCL, London, UK Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia Anglicare, Castle Hill Sydney, NSW, Australia School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia The Cooperative Research Centre for Mental Health, Carlton South, Australia Australian Alzheimer's Research Foundation, Nedlands, WA, Australia ADx NeuroSciences, Gent, Belgium Molecular Imaging and Therapy Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, Netherlands Biomarkable, Gent, Belgium |
Issue Date: | 11-Jan-2021 | Date: | 2021 | Publication information: | Translational Psychiatry 2021;11(1): 27 | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/25666 | DOI: | 10.1038/s41398-020-01137-1 | ORCID: | 0000-0003-4877-1958 0000-0002-3573-1554 0000-0003-0341-7445 0000-0003-3930-4354 0000-0002-1890-4193 0000-0002-4828-9363 |
Journal: | Translational Psychiatry | PubMed URL: | 33431793 | Type: | Journal Article | Subjects: | Alzheimer's disease |
Appears in Collections: | Journal articles |
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