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Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer's disease.
BMC Med. 2021 11 15; 19(1):264.BM

Abstract

BACKGROUND

The most common biomarkers of Alzheimer's disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB).

METHODS

RNA samples were extracted from the participant's blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity.

RESULTS

In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB.

CONCLUSIONS

This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD.

Links

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Authors+Show Affiliations

Jia L
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.
Zhu M
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.
Yang J
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.
Pang Y
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.
Wang Q
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.
Li Y
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.
Li T
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.
Li F
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.
Wang Q
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.
Li Y
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.
Wei Y
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.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersHumansMicroRNAsPeptide FragmentsPilot Projectstau Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34775974

Citation

Jia, Longfei, et al. "Prediction of P-tau/Aβ42 in the Cerebrospinal Fluid With Blood microRNAs in Alzheimer's Disease." BMC Medicine, vol. 19, no. 1, 2021, p. 264.
Jia L, Zhu M, Yang J, et al. Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer's disease. BMC Med. 2021;19(1):264.
Jia, L., Zhu, M., Yang, J., Pang, Y., Wang, Q., Li, Y., Li, T., Li, F., Wang, Q., Li, Y., & Wei, Y. (2021). Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer's disease. BMC Medicine, 19(1), 264. https://doi.org/10.1186/s12916-021-02142-x
Jia L, et al. Prediction of P-tau/Aβ42 in the Cerebrospinal Fluid With Blood microRNAs in Alzheimer's Disease. BMC Med. 2021 11 15;19(1):264. PubMed PMID: 34775974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer's disease. AU - Jia,Longfei, AU - Zhu,Min, AU - Yang,Jianwei, AU - Pang,Yana, AU - Wang,Qi, AU - Li,Ying, AU - Li,Tingting, AU - Li,Fangyu, AU - Wang,Qigeng, AU - Li,Yan, AU - Wei,Yiping, Y1 - 2021/11/15/ PY - 2021/06/07/received PY - 2021/09/27/accepted PY - 2021/11/15/entrez PY - 2021/11/16/pubmed PY - 2021/11/24/medline KW - Alzheimer’s disease KW - Biomarker KW - Dementia KW - Diagnosis KW - MicroRNA SP - 264 EP - 264 JF - BMC medicine JO - BMC Med VL - 19 IS - 1 N2 - BACKGROUND: The most common biomarkers of Alzheimer's disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: RNA samples were extracted from the participant's blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity. RESULTS: In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB. CONCLUSIONS: This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD. SN - 1741-7015 UR - https://www.unboundmedicine.com/medline/citation/34775974/Prediction_of_P_tau/Aβ42_in_the_cerebrospinal_fluid_with_blood_microRNAs_in_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -