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Browsing by Author "Leuzy, Antoine"
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Item Blood-based biomarkers for Alzheimer's disease(EMBO Press, 2022) Leuzy, Antoine; Mattsson-Carlgren, Niklas; Palmqvist, Sebastian; Janelidze, Shorena; Dage, Jeffrey L.; Hansson, Oskar; Neurology, School of MedicineNeurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever‐increasing role in research, clinical trials, and in the clinical work‐up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)‐based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra‐sensitive assays, the levels of pathological brain‐ and AD‐related proteins can now be measured in blood, with recent work showing promising results. Plasma P‐tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with Aβ42/Aβ40. Though not AD‐specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of disease‐modifying therapies. This review provides an overview of the progress achieved thus far using AD blood‐based biomarkers, highlighting key areas of application and unmet challenges.Item Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau(Wiley, 2022-02) Janelidze, Shorena; Palmqvist, Sebastian; Leuzy, Antoine; Stomrud, Erik; Verberk, Inge M.W.; Zetterberg, Henrik; Ashton, Nicholas J.; Pesini, Pedro; Sarasa, Leticia; Allué, José Antonio; Teunissen, Charlotte E.; Dage, Jeffrey L.; Blennow, Kaj; Mattsson-Carlgren, Niklas; Hansson, Oskar; Neurology, School of MedicineIntroduction: We studied usefulness of combining blood amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)217, and neurofilament light (NfL) to detect abnormal brain Aβ deposition in different stages of early Alzheimer's disease (AD). Methods: Plasma biomarkers were measured using mass spectrometry (Aβ42/Aβ40) and immunoassays (p-tau217 and NfL) in cognitively unimpaired individuals (CU, N = 591) and patients with mild cognitive impairment (MCI, N = 304) from two independent cohorts (BioFINDER-1, BioFINDER-2). Results: In CU, a combination of plasma Aβ42/Aβ40 and p-tau217 detected abnormal brain Aβ status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p-tau217 alone or Aβ42/Aβ40 and p-tau217 had similar AUCs (0.86-0.88); however, the latter showed improved model fit. The models were implemented in an online application providing individualized risk assessments (https://brainapps.shinyapps.io/PredictABplasma/). Discussion: A combination of plasma Aβ42/Aβ40 and p-tau217 discriminated Aβ status with relatively high accuracy, whereas p-tau217 showed strongest associations with Aβ pathology in MCI but not in CU.