Identify biological Alzheimer’s disease using a novel nucleic acid–linked protein immunoassay

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub>) 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-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub> 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-tau<sub>217</sub> 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, <i>P</i> < 0.0001) and tau-PET (area under the receiver operating characteristic curve = 0.939; 95% confidence interval = 0.909 to 0.969, <i>P</i> < 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.

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Journal
Brain Communications
Published
2024-12-24
DOI
https://doi.org/10.1093/braincomms/fcaf004
Citations
9
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
2.94

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article

Identify biological Alzheimer’s disease using a novel nucleic acid–linked protein immunoassay

Serge Gauthier, Tharick Ali Pascoal, Guglielmo Di Molfetta, Joseph Therriault et al.
9 citations
Brain Communications
Alzheimer's disease research and treatments
2.94
article

Identify biological Alzheimer’s disease using a novel nucleic acid–linked protein immunoassay

Serge Gauthier, Tharick Ali Pascoal, Guglielmo Di Molfetta, Joseph Therriault, Nicholas James Ashton, Richard Isaacson, Jaime Fernández Arias, Sulantha Mathotaarachchi, Nesrine Rahmouni, Andréa Lessa Benedet, Arthur C. Macedo, Ilaria Pola, Tevy Chan, Stijn Servaes, Yi‐Ting Wang, Firoza Zubeida Lussier, Cécile Tissot, Kaj Blennow, Henrik Zetterberg, Étienne Aumont, Pedro Rosa‐Neto, Seyyed Ali Hosseini, Jenna Stevenson, Kübra Tan
article en
9 citations

Abstract

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub>) 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-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub> 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-tau<sub>217</sub> 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, <i>P</i> < 0.0001) and tau-PET (area under the receiver operating characteristic curve = 0.939; 95% confidence interval = 0.909 to 0.969, <i>P</i> < 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.

Brain CommunicationsVol. 7(1)
University of Science and Technology of China (CN), Montreal Neurological Institute and Hospital (CA), University of Wisconsin–Madison (US), Lawrence Berkeley National Laboratory (US), University of Pittsburgh (US), King's College London (GB), Cornell University (US), Stavanger University Hospital (NO), Sahlgrenska University Hospital (SE), Centre for Mental Health (GB), Sorbonne Université (FR), Presbyterian Hospital (US), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), Institut du Cerveau (FR), University College London (GB), McGill University (CA), Florida Atlantic University (US), University of Gothenburg (SE)
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
Reduced inequalities
Openalex Percentile: Top 8%
Alzheimer's disease research and treatments
2.94
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