Liu L, Kwak H, Lawton TL, Jin SX, Meunier AL, Dang Y, Ostaszewski B, Pietras AC, Stern AM, Selkoe DJ. An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma. Alzheimers Dement. 2021 Sep 22; PubMed.

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  1. Selkoe and co-workers present a new immunoassay for the quantification of Aβ oligomers in human CSF and plasma. After showing the specificity of two new oAβ-selective antibodies, they perform a thorough validation of this ultra-sensitive oAβ immunoassay, as well as the first results showing that it works to accurately quantify these key species of AD pathogenesis.

    This assay will be an important tool to explore the pathophysiological role of oAβ directly in AD patients and in longitudinal studies on unimpaired elderly at risk for AD. Interesting outcomes may include how well plasma and CSF levels of oAβ correlate, and in which way plasma/CSF oAβ levels are associated with brain amyloidosis assessed by PET, specifically if a change in oAβ levels is evident before the PET signal reaches the threshold for positivity. Further, given the synaptotoxicity of oAβ shown in animal studies, data on how early in the AD continuum plasma/CSF oAβ levels change as compared to CSF levels of synaptic biomarkers would be exciting. In this respect, the finding in the present study of strong correlations between CSF oAβ levels and both CSF T-tau and P-tau181 is intriguing.

    Nevertheless, an important piece has been added to the AD biomarker toolbox, giving promise on future important mechanistic insights on the early stages of AD pathophysiology.

    View all comments by Kaj Blennow

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