. Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis. Neurology. 2020 Apr 14;94(15):e1580-e1591. Epub 2020 Mar 16 PubMed.


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  1. The study is very well-performed and corroborates earlier studies showing that adding plasma Aβ42/40 to an algorithm that includes age, sex, APOE genotype, and clinical diagnosis somewhat improves the ability of the model to predict amyloid positivity. Most importantly, the diagnostic value of plasma Aβ42/40 does not change with disease stage, and as shown in the present study the performance does not really change with time (from 18 months to 53 months from baseline). Consequently, plasma Aβ42/40 should perform as well in cognitively unimpaired as in cognitively impaired populations, which has previously been shown (e.g., Palmqvist et al., 2019). 

    It is interesting to note that a combination of plasma Ab42/40 and plasma p-tau could be superior to any of these markers alone when detecting amyloid pathology, as we recently indicated (Janelidze et al., 2020, Supplementary Table 4), but further studies are needed.


    . Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease-Related β-Amyloid Status. JAMA Neurol. 2019 Jun 24; PubMed.

    . Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease. Nat Commun. 2020 Apr 3;11(1):1683. PubMed.

  2. This is a well-written study on plasma Aβ42/Aβ40 as a biomarker for brain Aβ status. It is encouraging to see another study demonstrating that measurement of plasma Aβ42/Aβ40 can be used to inform on Aβ status, even in the preclinical stage of the disease. This bodes well for using plasma biomarkers to improve clinical trial design, and perhaps also in clinical practice in the future, in order to identify individuals with AD, independent of clinical stage.

    This study showed robust performance of the assay at three different time points. In the future, it would be interesting to also see associations between longitudinal trajectories of plasma biomarkers and Aβ status. For example, can reductions in plasma Aβ42/Aβ40 over time be used as a sensitive marker to identify incipient Aβ pathology?

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