Longitudinal evaluation of the natural history of amyloid-β in plasma and brain

Samantha Burnham, Noelia Fandos, Christopher Fowler, Virginia Perez-Grijalba, Vincent Doré, James D Doecke, Rosita Shishegar, Timothy Cox, Jürgen Fripp, Christopher Rowe, Manuel Sarasa, Colin L. Masters, Pedro Pesini, Victor L Villemagne

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Plasma amyloid-β peptide concentration has recently been shown to have high accuracy to predict amyloid-β plaque burden in the brain. These amyloid-β plasma markers will allow wider screening of the population and simplify and reduce screening costs for therapeutic trials in Alzheimer’s disease. The aim of this study was to determine how longitudinal changes in blood amyloid-β track with changes in brain amyloid-β. Australian Imaging, Biomarker and Lifestyle study participants with a minimum of two assessments were evaluated (111 cognitively normal, 7 mild cognitively impaired, 15 participants with Alzheimer’s disease). Amyloid-β burden in the brain was evaluated through PET and was expressed in Centiloids. Total protein amyloid-β 42/40 plasma ratios were determined using ABtest® assays. We applied our method for obtaining natural history trajectories from short term data to measures of total protein amyloid-β 42/40 plasma ratios and PET amyloid-β. The natural history trajectory of total protein amyloid-β 42/40 plasma ratios appears to approximately mirror that of PET amyloid-β, with both spanning decades. Rates of change of 7.9% and 8.8%, were observed for total protein amyloid-β 42/40 plasma ratios and PET amyloid-β, respectively. The trajectory of plasma amyloid-β preceded that of brain amyloid-β by a median value of 6 years (significant at 88% confidence interval). These findings, showing the tight association between changes in plasma and brain amyloid-β, support the use of plasma total protein amyloid-β 42/40 plasma ratios as a surrogate marker of brain amyloid-β. Also, that plasma total protein amyloid-β 42/40 plasma ratios has potential utility in monitoring trial participants, and as an outcome measure.
Original languageEnglish
Number of pages7
JournalBrain Communications
Volume2
Issue number1
DOIs
Publication statusPublished - 14 Apr 2020
Externally publishedYes

Keywords

  • plasma amyloid
  • Alzheimer's disease
  • amyloid imaging
  • aging

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