Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study
| Autor: | Lawren VandeVrede, Amy Wolf, Elisabeth H. Thijssen, Joel H. Kramer, Howard J. Rosen, Renaud La Joie, Corrina Fonseca, Kaj Blennow, Yann Cobigo, Andreas Jeromin, Marie-Anne Valentin, Adam L. Boxer, Oskar Hansson, Lili Yu, Salvatore Spina, Niklas Mattsson-Carlgren, Amelia Strom, Bradley F. Boeve, Bruce L. Miller, Charlotte E. Teunissen, Jeffrey L. Dage, William W. Seeley, Lea T. Grinberg, Arvind Kinhikar, Gil D. Rabinovici, Argentina Lario Lago, Agnieszka Kieloch, Leonardo Iaccarino, Nicholas K. Proctor, Treatment for Frontotemporal Lobar Degeneration investigators, Rajeev Sivasankaran, Hilary W. Heuer, Julio C. Rojas, Danielle Graham, Suzanne L. Baker, Isabel E. Allen, Henrik Zetterberg |
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| Přispěvatelé: | Laboratory Medicine, Obstetrics and gynaecology, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation |
| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Aging Disease Neurodegenerative Alzheimer's Disease Primary progressive aphasia Diagnosis 80 and over 2.1 Biological and endogenous factors Medicine Aetiology Phosphorylation Aged 80 and over screening and diagnosis Frontotemporal lobar degeneration Middle Aged Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators Frontotemporal Dementia (FTD) Detection Neurological Biomedical Imaging Female 4.2 Evaluation of markers and technologies Frontotemporal dementia Adult medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences tau Proteins Progressive supranuclear palsy Diagnosis Differential Rare Diseases Clinical Research Alzheimer Disease Predictive Value of Tests Internal medicine mental disorders Acquired Cognitive Impairment Humans Dementia Cognitive Dysfunction Aged Retrospective Studies Neurology & Neurosurgery Amyloid beta-Peptides business.industry Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Posterior cortical atrophy medicine.disease Brain Disorders Positron-Emission Tomography Differential Neurology (clinical) Frontotemporal Lobar Degeneration Differential diagnosis business Biomarkers |
| Zdroj: | The Lancet Neurology, 20(9), 739-752. Lancet Publishing Group Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators 2021, ' Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study ', The Lancet Neurology, vol. 20, no. 9, pp. 739-752 . https://doi.org/10.1016/S1474-4422(21)00214-3 The Lancet. Neurology, vol 20, iss 9 |
| ISSN: | 1474-4422 |
| Popis: | Background: Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes. Methods: In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18–99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test. Findings: Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, pdiff=0·31) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0·96 [0·92–1·00] for p-tau217, AUC=0·91 [0·82–1·00] for p-tau181; p diff=0·22). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0·93 [0·91–0·96] for p-tau217, AUC=0·91 [0·88–0·94] for p-tau181; p diff=0·01). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0·91 [0·88–0·94]) than was p-tau181 (n=214, AUC=0·89 [0·86–0·93]; p diff=0·049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0·80 vs r=0·72; p diff |
| Databáze: | OpenAIRE |
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