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The Aβ42/Aβ40 ratio in plasma is associated with amyloid‐PET status and rate of progression in individuals with subjective cognitive decline: The Fundació ACE Healthy Brain Initiative
Author(s) -
de Rojas Itziar,
Fandos Noelia,
Romero Judith,
Pesini Pedro,
Marquié Marta,
Tartari Juan Pablo,
Sanabria Angela,
SotolongoGrau Oscar,
Ruiz Agustin,
Boada Mercè,
Sarasa Manuel
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045780
Subject(s) - positron emission tomography , medicine , cognitive decline , mann–whitney u test , apolipoprotein e , cognitive impairment , psychology , pittsburgh compound b , nuclear medicine , disease , dementia
Background Cumulative data suggest that subjective cognitive decline (SCD) could be an early clinical manifestation of Alzheimer’s disease (AD). The performance of blood based AD‐related biomarkers at this early stage of the disease continuum has not been sufficiently studied yet. Method We explored the association between total Aβ42 to total Aβ40 ratio in plasma (TP42/40) assessed by ABtest (Araclon Biotech) and cortical β‐amyloid assessed by Florbetaben positron emission tomography (FBB‐PET, Life Molecular Imaging) scan in 162 cases of SCD from the Fundació ACE Healthy Brain Initiative (FACEHBI) with plasma and FBB‐PET data at baseline (V0) and two years follow‐up (V2) visits. All plasma samples were analyzed simultaneously at the time of V2. Cut‐off for PET‐FBB positivity was established at a global standardized uptake volume ratio (SUVR)>1.45. Result TP42/40 was significantly lower in FBB‐PET‐ve) than in FBB‐PET+ve group at both time points (Mann‐Whitney test P<0.0001). The AUC in the ROC analysis for the relevant demographic variables (age and APOE genotype) to discriminate FBB‐PET status at V0 and V2 was 80% and 83%, respectively. Those values increased significantly (P<0.01) up to 90% and 92%, respectively, when TP42/40 was included as a predictive variable within the model. The performance parameters of TP42/40 to discriminate FBB‐PET status in V0∼V2 were SEN 1.0∼0.94, SPE 0.49∼0.42, PPV 0.16∼0.15 and NPV 1.0∼0.98, respectively. Caution should be exerted when interpreting these values because they could be biased given the very low prevalence of FBB‐PET+ve (8.6%) in this early population, at the current SUVR cut‐off. Nevertheless, in a recruiting scenario targeting FBB‐PET+ve individuals with SCD, a pre‐screening step based on TP42/40 could save 46%∼34% of PET scans. Furthermore, those individuals with a TP42/40 ratio in the lowest quartile at V0 showed significantly (P<0.01) greater increases of FBB‐PET SUVR at V2 than those with a V0 plasma ratio in the two upper quartiles. Conclusion TP42/40 is consistently associated with cortical β‐amyloid burden assessed by FBB‐PET in individuals with SCD. The TP42/40 could be a useful tool helping in the recruitment of SCD individuals with preclinical Alzheimer’s.