Abstract:
:Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Karikari TK,Benedet AL,Ashton NJ,Lantero Rodriguez J,Snellman A,Suárez-Calvet M,Saha-Chaudhuri P,Lussier F,Kvartsberg H,Rial AM,Pascoal TA,Andreasson U,Schöll M,Weiner MW,Rosa-Neto P,Trojanowski JQ,Shaw LM,Blennow K,Zdoi
10.1038/s41380-020-00923-zsubject
Has Abstractpub_date
2020-10-26 00:00:00eissn
1359-4184issn
1476-5578pii
10.1038/s41380-020-00923-zpub_type
杂志文章abstract::Although inherited DNA sequences have a well-demonstrated role in psychiatric disease risk, for even the most heritable mental disorders, monozygotic twins are discordant at a significant rate. The genetic variation associated with mental disorders has heretofore been based on the search for rare or common variation i...
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pub_type: 杂志文章
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journal_title:Molecular psychiatry
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