Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline

Kazuhiko Uchida; Liu Shan; Hideaki Suzuki; Yo Tabuse; Yoshinori Nishimura; Yoshihiro Hirokawa; Katsuyoshi Mizukami; Hiroyasu Akatsu; Kohji Meno; Takashi Asada

doi:10.1016/j.dadm.2015.04.003

Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline

Alzheimers Dement (Amst). 2015 Jun 15;1(2):270-80. doi: 10.1016/j.dadm.2015.04.003. eCollection 2015 Jun.

Authors

Affiliations

¹ 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.
² 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.
³ Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Research Division, MCBI. Inc., Ibaraki, Japan.
⁴ Uji Hospital, Uji, Kyoto, Japan.
⁵ Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
⁶ Fukusimura Hospital, Toyohashi, Aichi, Japan.

Abstract

Introduction: 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.

Discussion: A set of sequester proteins could be blood-based biomarkers for assessment of early stages of cognitive decline.

Keywords: Alzheimer's disease; Apolipoprotein; Biomarker; Complement system; Diagnostics; Mild cognitive impairment; Transthyretin.