Identify biological Alzheimer’s disease using a novel nucleic acid–linked protein immunoassay
Year: 2024
Type: article
Abstract: Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer’s disease. Specifically, phosphorylated-tau variants (p-tau181, p-tau217 and p-tau231) are promising biomarkers for identifying Alzheimer’s disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer’s disease research field. A novel proteomic technology—NUcleic acid Linked Immuno-Sandwich Assay (NULISA)—was developed to improve the sensitivity of traditional proximity ligation assays and offer a comprehensive outlook for 120 protein biomarkers in neurodegenerative diseases. Due to the relative novelty of the NULISA technology in quantifying Alzheimer’s disease biomarkers, validation through comparisons with more established methods is required. The main objective of the current study was to determine the capability of p-tau variants quantified using NULISA for identifying abnormal amyloid-β and tau pathology. We assessed 397 participants [mean (standard deviation) age, 64.8 (15.7) years; 244 females (61.5%) and 153 males (38.5%)] from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort where participants had plasma measurements of p-tau181, p-tau217 and p-tau231 from NULISA and single molecule arrays immunoassays. Participants also underwent neuroimaging assessments, including structural MRI, amyloid-PET and tau-PET. Our findings suggest an excellent agreement between plasma p-tau variants quantified using NULISA and single molecule arrays immunoassays. Plasma p-tau217 measured with NULISA shows excellent discriminative accuracy for abnormal amyloid-PET (area under the receiver operating characteristic curve = 0.918, 95% confidence interval = 0.883 to 0.953, P < 0.0001) and tau-PET (area under the receiver operating characteristic curve = 0.939; 95% confidence interval = 0.909 to 0.969, P < 0.0001). It also presents the capability for differentiating tau-PET staging. Validation of the NULISA-measured plasma biomarkers adds to the current analytical methods for Alzheimer’s disease diagnosis, screening and staging and could potentially expedite the development of a blood-based biomarker panel.
Source: Brain Communications
Authors: Yi-Ting Wang, Nicholas J Ashton, Joseph Therriault, Andréa L Benedet, Arthur C Macedo, Ilaria Pola, Etienne Aumont, Guglielmo Di Molfetta, Jaime Fernandez-Arias, Kubra Tan, Nesrine Rahmouni, Stijn Johannes G Servaes, Richard Isaacson, Tevy Chan, Seyyed Ali Hosseini, Cécile Tissot, Sulantha Mathotaarachchi, Jenna Stevenson, Firoza Z Lussier, Tharick A Pascoal, Serge Gauthier, Kaj Blennow, Henrik Zetterberg, Pedro Rosa-Neto
Institutions: Montreal Neurological Institute and Hospital, McGill University Research Centre for Studies in Aging, McGill University, King's College London, South London and Maudsley NHS Foundation Trust, Stavanger University Hospital, NIHR Maudsley Biomedical Research Centre, University of Gothenburg, Weill Cornell Medicine, Florida Atlantic University, Lawrence Berkeley National Laboratory, University of Pittsburgh, University of Science and Technology of China, Sahlgrenska University Hospital, Sorbonne Université, Institut des Sciences Moléculaires, Pitié-Salpêtrière Hospital, Institut du Cerveau, University of Wisconsin–Madison, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,095
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, McGill University, Fondation Brain Canada, Stiftelsen för Gamla Tjänarinnor, Weston Brain Institute, EU Joint Programme – Neurodegenerative Disease Research, Consortium canadien en neurodégénérescence associée au vieillissement, National Institute for Health and Care Research, University College London, European Commission, Hjärnfonden, Vetenskapsrådet, UK Dementia Research Institute, Montreal Neurological Institute and Hospital, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Fonds de Recherche du Québec - Santé, National Institute on Aging
Awards: G1088883541, G1373393710, The Alzheimer’s Association quality control (QC) program for CSF and plasma biomarkers - Continuation, G150733400, G1588116593, G1625201577, G1771944843, G1802301745, G1833008592, Understanding Alzheimer Blood Biomarkers for Tau Pathology, G201353144, G2104733190, G2308068485, G235135605, G237833635, G2385484910, G2543812357, The Alzheimer biomarker toolbox – use in pathogenic studies, diagnostics and theragnostics, G2841269746, G2879339865, G292763017, G3027168043, G3167845995, Fluid biomarkers for neurodegenerative dementias, In vivo quantification of biomarker progression on the APP-RAT model, G3914690605, G4181470480, G4260843567, G432431387, G434337789, G4377393254, G4729658625, G499080294, G5040492720, G506008078, G516766298, Tau pathology in Alzheimer´s - understanding pathophysiology through biomarkers in blood and CSF, Fluid biomarkers for neurodegenerative dementias, G5544413620, G5813287008, G5880387862, G5901863754, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6236917951, G639136054, G6522198425, G6532618440, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6745400708, G691317373, G7077458143, G7764010130, G791739130, G8263961129, Arizona Alzheimer's Disease Research Center, G915560672
OpenAlex ID: W4406138917