1. Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome
- Author
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VandeVrede, Lawren, La Joie, Renaud, Thijssen, Elisabeth H, Asken, Breton M, Vento, Stephanie A, Tsuei, Torie, Baker, Suzanne L, Cobigo, Yann, Fonseca, Corrina, Heuer, Hilary W, Kramer, Joel H, Ljubenkov, Peter A, Rabinovici, Gil D, Rojas, Julio C, Rosen, Howie J, Staffaroni, Adam M, Boeve, Brad F, Dickerson, Brad C, Grossman, Murray, Huey, Edward D, Irwin, David J, Litvan, Irene, Pantelyat, Alexander Y, Tartaglia, Maria Carmela, Dage, Jeffrey L, and Boxer, Adam L
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Acquired Cognitive Impairment ,Clinical Trials and Supportive Activities ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Rare Diseases ,Neurodegenerative ,Clinical Research ,Alzheimer's Disease ,Brain Disorders ,Dementia ,Biomedical Imaging ,Neurological ,Adult ,Humans ,Female ,Aged ,Male ,Alzheimer Disease ,Corticobasal Degeneration ,Cohort Studies ,Bayes Theorem ,Supranuclear Palsy ,Progressive ,Amyloid beta-Peptides ,Frontotemporal Lobar Degeneration ,Frontotemporal Dementia ,Positron-Emission Tomography ,Biomarkers ,Atrophy ,tau Proteins - Abstract
ImportancePlasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology.ObjectiveTo validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS.Design, setting, and participantsThis multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort.Main outcome and measuresPlasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling.ResultsOf 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P
- Published
- 2023