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Title: Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease.
Austin Authors: 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
Affiliation: UK Dementia Research Institute at UCL, London, UK
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
Department of Psychiatry, University of Pittsburgh, Pennsylvania, USA
Centre for Healthy Ageing, Health Future Institute, Murdoch University, Murdoch, Western Australia, Australia
Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia
School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia
The Cooperative Research Centre for Mental Health, Carlton South, Australia
KaRa Institute of Neurological Disease, Macquarie Park, Australia
Macquarie Business School, Macquarie University, North Ryde, New South Wales, Australia
Department of Mathematics & Statistics, Curtin University, Bentley, Western Australia, Australia
Molecular Imaging and Therapy
College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia
eHealth, CSIRO Health and Biosecurity, Herston, Queensland, Australia
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
ADx NeuroSciences, Gent, Belgium
Issue Date: Jun-2022 2021-09-08
Publication information: Alzheimer's & dementia : the journal of the Alzheimer's Association 2022; 18(6): 1141-1154
Abstract: 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). Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis. 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. These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
DOI: 10.1002/alz.12447
Journal: Alzheimer's & Dementia
PubMed URL: 34494715
Type: Journal Article
Subjects: Alzheimer's disease
amyloid beta
blood biomarkers
brain amyloid beta
glial fibrillary acidic protein
longitudinal monitoring
neurofilament light
preclinical Alzheimer's disease
single molecule array
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