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Plasma phosphorylat...
Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.
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- Thijssen, Elisabeth H (author)
- Academic Medical Center of University of Amsterdam (AMC),University of California, San Francisco
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- La Joie, Renaud (author)
- University of California, San Francisco
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- Strom, Amelia (author)
- University of California, San Francisco
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- Fonseca, Corrina (author)
- University of California, San Francisco
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- Iaccarino, Leonardo (author)
- University of California, San Francisco
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- Wolf, Amy (author)
- University of California, San Francisco
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- Spina, Salvatore (author)
- University of California, San Francisco
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- Allen, Isabel E (author)
- University of California, San Francisco
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- Cobigo, Yann (author)
- University of California, San Francisco
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- Heuer, Hilary (author)
- University of California, San Francisco
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- VandeVrede, Lawren (author)
- University of California, San Francisco
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- Proctor, Nicholas K (author)
- Eli Lilly and Company
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- Lago, Argentina Lario (author)
- University of California, San Francisco
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- Baker, Suzanne (author)
- Lawrence Berkeley National Laboratory
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Sivasankaran, Rajeev (author)
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Kieloch, Agnieszka (author)
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Kinhikar, Arvind (author)
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Yu, Lili (author)
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Valentin, Marie-Anne (author)
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Jeromin, Andreas (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University College London,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Mattsson-Carlgren, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital
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- Graham, Danielle (author)
- Biogen, Inc.
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital
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Kramer, Joel H (author)
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- Grinberg, Lea T (author)
- University of California, San Francisco
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- Seeley, William W (author)
- University of California, San Francisco
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- Rosen, Howard (author)
- University of California, San Francisco
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- Boeve, Bradley F (author)
- Mayo Clinic Minnesota
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- Miller, Bruce L (author)
- University of California, San Francisco
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- Teunissen, Charlotte E (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Rabinovici, Gil D (author)
- University of California, San Francisco
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- Rojas, Julio C (author)
- University of California, San Francisco
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- Dage, Jeffrey L (author)
- Eli Lilly and Company
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- Boxer, Adam L (author)
- University of California, San Francisco
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(creator_code:org_t)
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- 2021
- 2021
- English.
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In: The Lancet. Neurology. - 1474-4465 .- 1474-4422. ; 20:9, s. 739-752
- Related links:
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http://dx.doi.org/10...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- 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.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.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, p<0·0001). Both p-tau217 and p-tau181 concentrations were increased in people with Alzheimer's disease syndromes (n=75, mean age 65 years [SD 10]) relative to cognitively unimpaired controls (n=118, mean age 61 years [SD 18]; AUC=0·98 [95% CI 0·95-1·00] for p-tau217, AUC=0·97 [0·94-0·99] for p-tau181; 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; pdiff=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; pdiff=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]; pdiff=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; pdiff<0·0001, n=230).Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology.US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Adult
- Aged
- Aged
- 80 and over
- Alzheimer Disease
- blood
- cerebrospinal fluid
- diagnosis
- Amyloid beta-Peptides
- metabolism
- Biomarkers
- blood
- Cognitive Dysfunction
- blood
- cerebrospinal fluid
- diagnosis
- Diagnosis
- Differential
- Female
- Frontotemporal Lobar Degeneration
- blood
- cerebrospinal fluid
- diagnosis
- Humans
- Male
- Middle Aged
- Phosphorylation
- physiology
- Positron-Emission Tomography
- Predictive Value of Tests
- Retrospective Studies
- tau Proteins
- blood
- cerebrospinal fluid
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Thijssen, Elisab ...
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La Joie, Renaud
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Strom, Amelia
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Fonseca, Corrina
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Iaccarino, Leona ...
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Wolf, Amy
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show more...
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Spina, Salvatore
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Allen, Isabel E
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Cobigo, Yann
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Heuer, Hilary
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VandeVrede, Lawr ...
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Proctor, Nichola ...
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Lago, Argentina ...
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Baker, Suzanne
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Sivasankaran, Ra ...
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Kieloch, Agniesz ...
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Kinhikar, Arvind
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Yu, Lili
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Valentin, Marie- ...
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Jeromin, Andreas
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Zetterberg, Henr ...
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Hansson, Oskar
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Mattsson-Carlgre ...
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Graham, Danielle
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Blennow, Kaj, 19 ...
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Kramer, Joel H
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Grinberg, Lea T
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Seeley, William ...
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Rosen, Howard
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Boeve, Bradley F
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Miller, Bruce L
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Teunissen, Charl ...
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Rabinovici, Gil ...
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Rojas, Julio C
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Dage, Jeffrey L
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Boxer, Adam L
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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The Lancet. Neur ...
- By the university
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University of Gothenburg
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Lund University