title: Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline.
abstract: BACKGROUND
  There are no blood-based biomarkers for cognitive decline in aging, or mild cognitive impairment (MCI) and Alzheimer's disease (AD). Cumulative evidence suggests that apolipoproteins, complement system, and transthyretin are involved in AD pathogenesis by sequestration of amyloid β. However, there is no clinical study to assess the utility of "sequester proteins" in risk assessment and/or diagnosis of MCI and AD.
  
  
  METHODS
  Serum levels of sequester proteins and their clinical potential in cognitive decline assessment were analyzed by longitudinal and cross-sectional studies using independent cohorts and were confirmed by a prospective study.
  
  
  RESULTS
  A combination of apolipoprotein A1, complement C3, and transthyretin achieved an area under the curve of 0.89 (sensitivity 91% and specificity 80%) in MCI versus healthy controls and also discriminated individuals with mild cognitive decline from healthy controls.
  
  
  CONCLUSIONS
  A set of sequester proteins could be blood-based biomarkers for assessment of early stages of cognitive decline.
authors.affiliation: Department of Molecular Biological Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Molecular Biological Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Liu
authors.initials: L
authors.lastname: Shan
authors.affiliation: Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Research Division, MCBI. Inc., Ibaraki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Research Division, MCBI. Inc., Ibaraki, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Tabuse
authors.affiliation: Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Research Division, MCBI. Inc., Ibaraki, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Uji Hospital, Uji, Kyoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirokawa
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mizukami
authors.affiliation: Fukusimura Hospital, Toyohashi, Aichi, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Research Division, MCBI. Inc., Ibaraki, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Meno
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asada
keywords: Alzheimer's disease; Apolipoprotein; Biomarker; Complement system; Diagnostics; Mild cognitive impairment; Transthyretin