title: Mass-Spectrometry-Based Method To Quantify in Parallel Tau and Amyloid β 1-42 in CSF for the Diagnosis of Alzheimer's Disease.
abstract: Alzheimer's disease (AD), the most common form of dementia, afflicts about 50 million people worldwide. Currently, AD diagnosis is primarily based on psychological evaluation and can only be confirmed post-mortem. Reliable and objective biomarkers for prognosis and diagnosis have been sought for years. Together, tau and amyloid β 1-42 (Aβ42) in cerebrospinal fluid (CSF) have been shown to provide good diagnostic sensitivity and specificity. Additionally, phosphorylated forms of tau, such as tau pS181, have also shown promising results. However, the measurement of such markers currently relies on antibody-based immunoassays that have shown variability, leading to discrepant results across laboratories. To date, mass spectrometry methods developed to evaluate CSF tau and Aβ42are not compatible. We present in this article the development of a mass-spectrometry-based method of quantification for CSF tau and Aβ42in parallel. The absolute concentrations of tau and Aβ42we measured are on average 50 ng/mL (7-130 ng/mL) and 7.1 ng/mL (3-13 ng/mL), respectively. Analyses of CSF tau and Aβ42, in a cohort of patients with AD, mild cognitive impairment, and healthy controls (30 subjects), provide significant group differences evaluated with ROC curves (AUC(control-AD)and AUC(control-MCI)= 1, AUC(MCI-AD)= 0.76), with at least equivalent diagnostic utility to immunoassay measurements in the same sample set. Finally, a significant and negative correlation was found between the tau and Aβ peptides ratio and the disease severity.
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Gwënaël
authors.identifier: 0000-0001-8485-4510
authors.initials: G
authors.lastname: Pottiez
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Tessandra
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aro
authors.affiliation: Department of Neurosciences, University of California at San Diego , San Diego, California 92093, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.affiliation: Department of Neurology, Oregon Health and Science University , Portland, Oregon 97239, United States.|Portland VA Medical Center , Portland, Oregon 97239, United States.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Northwest Network VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System , Seattle, Washington 98108, United States.|Department of Psychiatry and Behavioral Sciences, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, School of Medicine, University of Washington , Seattle, Washington 98104, United States.|Department of Pathology, Peking University Health Science Centre and Third Hospital , Beijing 100083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; Aβ42; SRM; amyloid β; biomarker; cerebrospinal fluid; diagnosis; mass spectrometry; tau