This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1
Tao Wang
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2153-7328
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease with the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) imbalance. Altered microRNAs (miRNA) associated with BACE1 may be potential biomarkers for aMCI diagnosis. The aims of this study were to find an effective diagnostic model for aMCI, and to explore the modulation of candidate miRNAs on BACE1 expression.
Methods: Plasma RNA was extracted from participants enrolled in China longitudinal aging study (CLAS). MiRNA profiling was performed using microarray sequencing on a discovery set, compromising five aMCI subjects that confirmed by 18F-Flutemetamol PET scan and five normal controls (NC). Quantitative reverse transcription PCR was used to validate the expression levels of differently expressed miRNAs on an analysis set (20 aMCI subjects and 10 NC). Diagnostic capability of candidate miRNAs was assessed in a validation set (40 aMCI subjects and 40 NC). Modulation of candidate miRNAs on BACE1 was explored in rat and human hippocampal neurons in vitro through transfection of miRNA mimics or inhibitor lentivirus.
Results: In discovery set, we verified 46 significantly differentially expressed miRNAs between aMCI and NC groups (P<0.05). Among these, 33 miRNAs were down-regulated and 13 miRNAs were up-regulated. In analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p also significantly decreased in aMCI group. Four miRNAs above and miR-107 which was found to decline in previous study were selected as potential biomarkers. A diagnostic model consists of five miRNAs above had an outstanding diagnostic accuracy (81.25%) to diagnose aMCI. Except for miR-134-3p, other four miRNAs modulated BACE1 expression and C-terminal fragments-beta production effectively in rat hippocampal neurons in vitro. Similar modulation of miR-1185-2-3p and miR-1909-3p were confirmed in human hippocampal neurons in vitro.
Conclusion: A diagnostic model consists of five plasma miRNAs could be novel biomarker for aMCI diagnosis. These miRNAs might be involved in pathogenesis of AD through regulating expression of BACE1.
Keywords
Amnestic mild cognitive impairment, Biomarker, MicroRNA, Early diagnosis, BACE1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cognitive Neuroscience
Learn more about our company.
This is a preprint. It has not completed peer review.
Research
Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1
Tao Wang
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2153-7328
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cognitive Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease with the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) imbalance. Altered microRNAs (miRNA) associated with BACE1 may be potential biomarkers for aMCI diagnosis. The aims of this study were to find an effective diagnostic model for aMCI, and to explore the modulation of candidate miRNAs on BACE1 expression.
Methods: Plasma RNA was extracted from participants enrolled in China longitudinal aging study (CLAS). MiRNA profiling was performed using microarray sequencing on a discovery set, compromising five aMCI subjects that confirmed by 18F-Flutemetamol PET scan and five normal controls (NC). Quantitative reverse transcription PCR was used to validate the expression levels of differently expressed miRNAs on an analysis set (20 aMCI subjects and 10 NC). Diagnostic capability of candidate miRNAs was assessed in a validation set (40 aMCI subjects and 40 NC). Modulation of candidate miRNAs on BACE1 was explored in rat and human hippocampal neurons in vitro through transfection of miRNA mimics or inhibitor lentivirus.
Results: In discovery set, we verified 46 significantly differentially expressed miRNAs between aMCI and NC groups (P<0.05). Among these, 33 miRNAs were down-regulated and 13 miRNAs were up-regulated. In analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p also significantly decreased in aMCI group. Four miRNAs above and miR-107 which was found to decline in previous study were selected as potential biomarkers. A diagnostic model consists of five miRNAs above had an outstanding diagnostic accuracy (81.25%) to diagnose aMCI. Except for miR-134-3p, other four miRNAs modulated BACE1 expression and C-terminal fragments-beta production effectively in rat hippocampal neurons in vitro. Similar modulation of miR-1185-2-3p and miR-1909-3p were confirmed in human hippocampal neurons in vitro.
Conclusion: A diagnostic model consists of five plasma miRNAs could be novel biomarker for aMCI diagnosis. These miRNAs might be involved in pathogenesis of AD through regulating expression of BACE1.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6