Re-evaluation of Soluble APP-α and APP-β in Cerebrospinal Fluid As Potential Biomarkers for Early Diagnosis of Dementia Disorders

Overview

Journal Biomark Res

Publisher Biomed Central

Date 2017 Oct 12

PMID 29018524

Citations 8

Authors

Wataru Araki

Kotaro Hattori

Kazutomi Kanemaru

Yuma Yokoi

Yoshie Omachi

Harumasa Takano

Masuhiro Sakata

Sumiko Yoshida

Tadashi Tsukamoto

Miho Murata

Yuko Saito

Hiroshi Kunugi

Yu-ichi Goto

Utako Nagaoka

Masahiro Nagao

Takashi Komori

Kunimasa Arima

Kenji Ishii

Shigeo Murayama

Hiroshi Matsuda

Hisateru Tachimori

Yumiko M Araki

Hidehiro Mizusawa

Affiliations

Soon will be listed here.

Abstract

Background: Because soluble (or secreted) amyloid precursor protein-β (sAPPβ) and -α (sAPPα) possibly reflect pathological features of Alzheimer's disease (AD), they are potential biomarker candidates for dementia disorders, including AD and mild cognitive impairment (MCI) due to AD (MCI-AD). However, controversial results have been reported regarding their alterations in the cerebrospinal fluid (CSF) of AD and MCI-AD patients. In this study, we re-assessed the utility of sAPPα and sAPPβ in CSF as diagnostic biomarkers of dementia disorders.

Methods: We used a modified and sensitive detection method to analyze sAPPs levels in CSF in four groups of patients: AD ( = 33), MCI-AD ( = 17), non-AD dementia ( = 27), and disease controls ( = 19). Phosphorylated tau (p-tau), total tau, and Aβ42 were also analyzed using standard methods.

Results: A strong correlation was observed between sAPPα and sAPPβ, consistent with previous reports. Both sAPPα and sAPPβ were highly correlated with p-tau and total tau, suggesting that sAPPs possibly reflect neuropathological changes in the brain. Levels of sAPPα were significantly higher in MCI-AD cases compared with non-AD and disease control cases, and those of sAPPβ were also significantly higher in MCI-AD and AD cases relative to other cases. A logistic regression analysis indicated that sAPPα and sAPPβ have good discriminative power for the diagnosis of MCI-AD.

Conclusions: Our findings collectively suggest that both sAPPs are pathologically relevant and potentially useful biomarkers for early and accurate diagnosis of dementia disorders. We also suggest that careful measurement is important in assessing the diagnostic utility of CSF sAPPs.

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