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Soluble APP-α and APP-β in cerebrospinal fluid as potential biomarkers for differential diagnosis of mild cognitive impairment

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Abstract

Objectives

Concentrations of soluble amyloid precursor proteins-α (sAPPα) and -β (sAPPβ) in cerebrospinal fluid (CSF) may reflect the neuropathology of Alzheimer’s disease (AD). We previously reported that the concentrations of both sAPPα and sAPPβ were significantly higher in patients with mild cognitive impairment (MCI) due to AD (MCI-AD) than in control subjects without cognitive impairment. The present study analyzed whether these sAPPs are useful in the differential diagnosis of MCI.

Methods

A modified and sensitive method was used to analyze concentrations of sAPPα and sAPPβ in CSF of patients with MCI-AD (n = 30) and MCI due to other causes (MCI-others) (n = 24). Phosphorylated tau (p-tau) and amyloid β-protein 42 (Aβ42) were also analyzed using standard methods.

Results

CSF concentrations of sAPPα and sAPPβ were significantly higher in the MCI-AD than in the MCI-others group (p < 0.001). Furthermore, concentrations of both sAPPα and sAPPβ were highly correlated with the concentration of p-tau, consistent with our previous report.

Conclusions

Measurement of both sAPPs in CSF using sensitive methods can be helpful in the precise differential diagnosis of patients with MCI.

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Acknowledgements

We thank Drs. Y. M. Araki, K. Ishii, H. Matsuda, Y. Goto, K. Wada, and Y. Takahashi for their kind cooperation and encouragement.

Funding

This work was supported by an Intramural Research Grant (30-3) for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry.

Author information

Authors and Affiliations

  1. Department of Demyelinating Disease and Aging, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan

    Wataru Araki

  2. Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan

    Kazutomi Kanemaru & Shigeo Murayama

  3. Medical Genome Center, NCNP, Kodaira, Tokyo, Japan

    Kotaro Hattori

  4. National Center Hospital, NCNP, Kodaira, Tokyo, Japan

    Tadashi Tsukamoto, Yuko Saito, Sumiko Yoshida, Harumasa Takano, Masuhiro Sakata, Yuma Yokoi, Yoshie Omachi & Hidehiro Mizusawa

  5. Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan

    Utako Nagaoka, Masahiro Nagao & Takashi Komori

  6. Department of Clinical Epidemiology, Translational Medical Center, NCNP, Kodaira, Tokyo, Japan

    Hisateru Tachimori

Authors
  1. Wataru Araki
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Corresponding author

Correspondence to Wataru Araki.

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The authors have no conflict of interest to disclose.

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The study has been approved by the appropriate institutional research ethics committee and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Araki, W., Kanemaru, K., Hattori, K. et al. Soluble APP-α and APP-β in cerebrospinal fluid as potential biomarkers for differential diagnosis of mild cognitive impairment. Aging Clin Exp Res 34, 341–347 (2022). https://doi.org/10.1007/s40520-021-01935-7

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  • DOI: https://doi.org/10.1007/s40520-021-01935-7

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