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The free plasma amyloid Aβ1–42/Aβ1–40 ratio predicts conversion to dementia for subjects with mild cognitive impairment with performance equivalent to that of the total plasma Aβ1–42/Aβ1–40 ratio. The BALTAZAR study

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  • Additional Information
    • Contributors:
      Université de Lille; Inserm; CHU Lille; Lille Neurosciences & Cognition (LilNCog) - U 1172; METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694; Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies URP_4468; Centre Hospitalier Régional Universitaire Montpellier CHRU Montpellier; Université de Montpellier UM; Institut de psychiatrie et neurosciences de Paris IPNP - U1266 Inserm; CHU Pitié-Salpêtrière AP-HP; Institut des Neurosciences de Montpellier INM; Groupe hospitalier Broca
    • Publication Date:
      2024
    • Collection:
      LillOA (Lille Open Archive - Université de Lille)
    • Abstract:
      Background and purpose Blood-based biomarkers are a non-invasive solution to predict the risk of conversion of mild cognitive impairment (MCI) to dementia. The utility of free plasma amyloid peptides (not bound to plasma proteins and/or cells) as an early indicator of conversion to dementia is still debated, as the results of studies have been contradictory. In this context, we investigated whether plasma levels of the free amyloid peptides Aβ1–42 and Aβ1–40 and the free plasma Aβ1–42/Aβ1–40 ratio are associated with the conversion of MCI to dementia, in particular AD, over three years of follow-up in a subgroup of the BALTAZAR cohort. We also compared their predictive value to that of total plasma Aβ1–42 and Aβ1–40 levels and the total plasma Aβ1–42/Aβ1–40 ratio. Methods The plasma Aβ1–42 and Aβ1–40 peptide assay was performed using the INNO-BIA kit (Fujirebio Europe). Free amyloid levels (defined by the amyloid fraction directly accessible to antibodies of the assay) were obtained with the undiluted plasma, whereas total amyloid levels were obtained after the dilution of plasma (1/3) with a denaturing buffer. Free and total Aβ1–42 and Aβ1–40 levels were measured at inclusion for a subgroup of participants (N = 106) with mild cognitive impairment (MCI) from the BALTAZAR study (a large-scale longitudinal multicenter cohort with a three-year follow-up). Associations between conversion and the free/total plasma Aβ1–42 and Aβ1–40 levels and Aβ1–42/Aβ1–40 ratio were analyzed using logistic and Cox Proportional Hazards models. Demographic, clinical, cognitive (MMSE, ADL and IADL), APOE, and MRI characteristics (relative hippocampal volume) were compared using non-parametric (Mann-Whitney) or parametric (Student) tests for quantitative variables and Chi-square or Fisher exact tests for qualitative variables. Results The risk of conversion to dementia was lower for patients in the highest quartile of free plasma Aβ1–42/Aβ1–40 (≥ 25.8%) than those in the three lower quartiles: hazard ratio = 0.36 (95% confidence ...
    • File Description:
      application/octet-stream; application/rdf+xml; charset=utf-8; application/pdf
    • Relation:
      Neurobiology of Disease; Neurobiol Dis; http://hdl.handle.net/20.500.12210/110067
    • Online Access:
      https://hdl.handle.net/20.500.12210/110067
    • Rights:
      Attribution-NonCommercial-NoDerivs 3.0 United States ; info:eu-repo/semantics/openAccess
    • Accession Number:
      edsbas.510A31F2