A blood mRNA panel that differentiates Alzheimer's disease from other dementia types

doi:10.1007/s00415-023-11558-9

. 2023 Jan 7.

doi: 10.1007/s00415-023-11558-9. Online ahead of print.

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types

Xiaofeng Fu^#¹, Changbiao Chu^#¹, Yana Pang¹, Huimin Cai¹, Ziye Ren¹, Longfei Jia²

Affiliations

¹ Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, China.
² Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, China. longfei@mail.ccmu.edu.cn.

^# Contributed equally.

PMID: 36611114
DOI: 10.1007/s00415-023-11558-9

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types

Xiaofeng Fu et al. J Neurol. 2023.

. 2023 Jan 7.

doi: 10.1007/s00415-023-11558-9. Online ahead of print.

Authors

Xiaofeng Fu^#¹, Changbiao Chu^#¹, Yana Pang¹, Huimin Cai¹, Ziye Ren¹, Longfei Jia²

Affiliations

¹ Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, China.
² Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, China. longfei@mail.ccmu.edu.cn.

^# Contributed equally.

PMID: 36611114
DOI: 10.1007/s00415-023-11558-9

Abstract

Background: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB).

Methods: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia.

Results: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3.

Conclusions: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.

Keywords: Alzheimer’s disease; Biomarker; Dementia; Diagnosis; mRNA.

References

1. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117. https://doi.org/10.1016/S0140-6736(05)67889-0 - DOI
1. Jack CJ, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB et al (2018) NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4):535–562. https://doi.org/10.1016/j.jalz.2018.02.018 - DOI
1. Ritchie K, Lovestone S (2002) The dementias. Lancet 360(9347):1759–1766. https://doi.org/10.1016/S0140-6736(02)11667-9 - DOI
1. Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ (2012) Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 8(9):518–530. https://doi.org/10.1038/nrneurol.2012.156 - DOI
1. Toden S, Zhuang J, Acosta AD, Karns AP, Salathia NS, Brewer JB et al (2020) Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing. Sci Adv. https://doi.org/10.1126/sciadv.abb1654 - DOI

Grant support

[1] Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117. https://doi.org/10.1016/S0140-6736(05)67889-0 - DOI

[2] Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117. https://doi.org/10.1016/S0140-6736(05)67889-0 - DOI

[3] Jack CJ, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB et al (2018) NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4):535–562. https://doi.org/10.1016/j.jalz.2018.02.018 - DOI

[4] Jack CJ, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB et al (2018) NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4):535–562. https://doi.org/10.1016/j.jalz.2018.02.018 - DOI

[5] Ritchie K, Lovestone S (2002) The dementias. Lancet 360(9347):1759–1766. https://doi.org/10.1016/S0140-6736(02)11667-9 - DOI

[6] Ritchie K, Lovestone S (2002) The dementias. Lancet 360(9347):1759–1766. https://doi.org/10.1016/S0140-6736(02)11667-9 - DOI

[7] Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ (2012) Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 8(9):518–530. https://doi.org/10.1038/nrneurol.2012.156 - DOI

[8] Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ (2012) Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 8(9):518–530. https://doi.org/10.1038/nrneurol.2012.156 - DOI

[9] Toden S, Zhuang J, Acosta AD, Karns AP, Salathia NS, Brewer JB et al (2020) Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing. Sci Adv. https://doi.org/10.1126/sciadv.abb1654 - DOI

[10] Toden S, Zhuang J, Acosta AD, Karns AP, Salathia NS, Brewer JB et al (2020) Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing. Sci Adv. https://doi.org/10.1126/sciadv.abb1654 - DOI