In:
Alzheimer's & Dementia, Wiley, Vol. 18, No. S6 ( 2022-12)
Abstract:
Technological advancements have made it possible to translate changes in cerebrospinal fluid (CSF) into promising plasma biomarkers, such as the amyloid β ratio (Aβ 42 /Aβ 40 ) and phosphorylated tau (p‐tau), but comparing CSF and plasma levels were often based on different technologies. Combining biomarkers have demonstrated a superior performance of the ratio of p‐tau over Aβ42 to discriminate Aβ‐positive (Aβ+) and Aβ‐negative (Aβ‐) groups in CSF, especially using automated immunoassay platforms, but has not yet been studied in plasma. Method In a subset of 155 MCI individuals of the BioFINDER‐1 study, from which 84 paired CSF‐plasma were available for analysis, Aβ 42 , Aβ 40 and p‐tau181 were determined using ADx Simoa assays (Thijssen et al, 2021; Bayoumy et al, 2021) in both fluids using the appropriate dilution factors. Result The intra‐run %CV was between 1.7 and 2.6% for both Aβ markers in CSF and plasma and was higher in plasma for p‐tau181 than in CSF with respectively 10.5 and 1.7%. Both CSF Aβ 42 , Aβ 40 and Aβ 42 /Aβ 40 were highly correlated to CSF Aβ measurements using the MSD platform: spearman ρ of 0.845; 0.828; and 0.882 for respectively for Aβ 42 , Aβ 40 and their ratio. In the paired CSF‐plasma analysis the strongest correlation was found for p‐tau181/Aβ 42 and p‐tau181 with respectively a ρ=0.689 and 0.616 and a significantly weaker correlation for Aβ 42 /Aβ 40 ratio (ρ=0.283). Defining an Aβ+ and an Aβ‐ subgroup by using a previously verified CSF Aβ 42 /Aβ 40 of 0.07, all plasma biomarkers could differentiate Aβ+ and Aβ‐ individuals. The highest AUC was observed for p‐tau181/ Aβ 42 , 0.806, significantly (p=0.0465) higher than p‐tau181 (0.784) and the Aβ 42 /Aβ 40 (0.688)(Fig 1). Conclusion Correlations in paired CSF‐plasma samples using the same technology are significant, but weak for some of them suggesting a different turnover of these analytes in these fluids. Nevertheless combining both well‐established pathological markers in plasma, p‐tau and Aβ 42 , may be a simple way to enhance early diagnosis based especially if automated immunoassay platforms are envisaged.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2201940-6
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