Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease

Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217,...

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Published inThe Journal of experimental medicine Vol. 217; no. 11
Main Authors Barthélemy, Nicolas R., Horie, Kanta, Sato, Chihiro, Bateman, Randall J.
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 02.11.2020
Subjects
Adult
Aged
Aged, 80 and over
Alzheimer Disease - blood
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - diagnostic imaging
Alzheimer Disease - pathology
Amyloid beta-Peptides - blood
Amyloid beta-Peptides - cerebrospinal fluid
Biomarkers - blood
Brain - diagnostic imaging
Brain - pathology
Brief Definitive Report
Case-Control Studies
Cohort Studies
Female
Humans
Male
Mass Spectrometry - methods
Middle Aged
Neuroscience
Phosphorylation
Plaque, Amyloid
Positron-Emission Tomography
Protein Isoforms
tau Proteins - blood
tau Proteins - cerebrospinal fluid
tau Proteins - chemistry
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Summary:Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms’ profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort (n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort (n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75).
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Disclosures: N.R. Barthélemy reported a patent to the US patent office for "blood-based assay for diagnosing and treating based on site-specific tau phosphorylation" pending, and a patent to the US patent office for "methods of diagnosing and treating based on site-specific tau phosphorylation" issued. Washington University and R.J. Bateman have equity ownership interest in C2N Diagnostics. R.J. Bateman and N.R. Barthélemy may receive royalty income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. R.J. Bateman receives income from C2N Diagnostics for serving on the scientific advisory board. K. Horie is a visiting scholar at Washington University and employed by Eisai Co., Ltd. K. Hori may receive income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. C. Sato may receive income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. R.J. Bateman reported "other" from C2N Diagnostics, personal fees from Eisai, AC Immune, Amgen, Pfizer, Hoffman LaRoche, and Janssen; and grants from AbbVie, Biogen, and Eli Lilly and Co. outside the submitted work. In addition, R.J. Bateman had a patent to "blood-based assay for diagnosing and treating based on site-specific tau phosphorylation" pending and a patent to "methods of diagnosing and treating based on site-specific tau phosphorylation" pending. Washington University and R.J. Bateman have equity ownership interest in C2N Diagnostics and may receive royalty income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics.
ISSN:0022-1007
1540-9538
1540-9538
DOI:10.1084/jem.20200861