Journal Article

Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

Janelidze, Shorena, Chen, Charles D., Ossenkoppele, Rik, He, Yingxin, Mattsson-Carlgren, Niklas, Rabinovici, Gil D., Salvadó, Gemma, Collij, Lyduine E., Benzinger, Tammie L. S., Palmqvist, Sebastian, La Joie, Renaud, Bateman, Randall J., Henson, Rachel L., Hansson, Oskar, Stomrud, Erik, Morris, John C., Li, Yan, Gordon, Brian A., Barthélemy, Nicolas R., Schindler, Suzanne E., Saef, Benjamin

2024

Overview

With the emergence of Alzheimer’s disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort ( n  = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort ( n  = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using positron emission tomography (PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area under the curve (AUC) for both between 0.95 and 0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95–0.98. In cognitively impaired subcohorts (BioFINDER-2: n  = 720; Knight ADRC: n  = 50), plasma %p-tau217 had an accuracy, a positive predictive value and a negative predictive value of 89–90% for Aβ PET and 87–88% for tau PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two-cutoffs approach. Blood plasma %p-tau217 demonstrated performance that was clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high-performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments. The performance of plasma %p-tau217 is clinically equivalent in classification of Aβ PET status and superior in classification of tau PET status compared to clinically used and FDA-approved CSF tests in cognitively impaired participants.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/53/2421 / 692/617/375/132/1283 / 692/700/139 / Alzheimer Disease / Alzheimer's disease / Amyloid beta-Peptides - cerebrospinal fluid / Biomarkers / Biomedical and Life Sciences / Biomedicine / Blood / Blood plasma / Blood tests / Cancer Research / Cerebrospinal fluid / Classification / Cognitive ability / Cognitive Dysfunction - cerebrospinal fluid / Cognitive Dysfunction - diagnosis / Dementia disorders / Emission analysis / Equivalence / FDA approval / Hematologic Tests / Humans / Immunoassays / Impairment / Infectious Diseases / Mass spectrometry / Mass spectroscopy / Metabolic Diseases / Mild cognitive impairment / Molecular Medicine / Neurodegenerative diseases / Neuroimaging / Neurosciences / Pathology / Plasma / Positron emission / Positron emission tomography / Research facilities / Tau protein / tau Proteins / β-Amyloid