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High performance plasma amyloid-β biomarkers for Alzheimer's disease.

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Affiliations

  • 1. Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
      Authors
    • Nakamura A 1
    • Kato T 1, 11
    • Ito K 1, 11
    • Yanagisawa K 1
    (4 authors)
  • 2. Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan.
      Authors
    • Kaneko N 2
    • Iwamoto S 2
    • Tanaka K 2
    (3 authors)
  • 3. Austin Health, Department of Molecular Imaging and Therapy, Center for PET, Heidelberg, Victoria 3084, Australia.
      Authors
    • Villemagne VL 3, 5
    • Doré V 3, 4
    • Rowe C 3, 5
    (3 authors)
  • 4. Health and Biosecurity, CSIRO, Brisbane 4029, Australia.
      Authors
    • Doecke J 4
    • Doré V 3, 4
    (2 authors)
  • 5. The Florey Institute, The University of Melbourne, Parkville 3010, Australia.
      Authors
    • Villemagne VL 3, 5
    • Fowler C 5
    • Li QX 5
    • Rowe C 3, 5
    • Masters CL 5
    (5 authors)
    • Show all (11)

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Nature, 31 Jan 2018, 554(7691):249-254
https://doi.org/10.1038/nature25456 PMID: 29420472 

A comment on this article appears in "Alzheimer disease: Blood amyloid-β successfully signals AD." Nat Rev Neurol. 2018 Apr;14(4):195.

Abstract 

To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease, supportive biomarker information is necessary. The only validated methods for identifying amyloid-β deposition in the brain-the earliest pathological signature of Alzheimer's disease-are amyloid-β positron-emission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable. Despite much effort, to our knowledge, no study has validated the clinical utility of blood-based amyloid-β markers. Here we demonstrate the measurement of high-performance plasma amyloid-β biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-β precursor protein (APP)669-711/amyloid-β (Aβ)1-42 and Aβ1-40/Aβ1-42 ratios, and their composites, to predict individual brain amyloid-β-positive or -negative status was determined by amyloid-β-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using 11C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-β burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-β-PET burden and levels of Aβ1-42 in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-β burden at an individual level. These plasma biomarkers also have cost-benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.

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Read article at publisher's site: https://doi.org/10.1038/nature25456

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