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Gerard Piñol-Ripoll
Hospital Universitari Santa Maria
Corresponding Author
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Background: Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.
Methods: To discover the miRNAs related to the rate of cognitive impairment, we analysed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after two years (<4 points (N=11) and ≥ 4 points (N=8)). The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N=53) with mild AD using RT-qPCR.
Results: In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r=-0.28; p=0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after two years (p=0.049).
Conclusion: Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after two years of follow-up.
Keywords
Alzheimer’s disease, Cognitive decline, miRNA, miR-342-5p
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- Table1.xlsx
Table 1. Characteristics of the study population that participated in the discovery and validation cohorts. SDC: Slow decline in cognition; FDC: Fast decline in cognition; MMSE: Mini-Mental State Examination; Aβ42: Amyloid beta 42; T-tau: Total tau protein; P-tau: Phosphorylated tau protein
- Supplementarydata.docx
Supplementary Figure 1. Quality control of TaqMan Low Density Array (TLDA) determinations. Number of determinations/missings. Supplementary Figure 2. Ct distribution of miRNAs in TLDA cards. Supplementary Figure 3. The expression stability of the selected endogenous controls characterized by means of GeNorm and Bestkeeper. Supplementary Table 1. miRNAs expressed differentially between FDC and SDC groups in the discovery cohort. Supplementary Figure 4. Ct distribution of miRNAs in RT-qPCR cohort. Supplementary Figure 5. Box plot diagram of the relative expression of miR-342-5p among AD patients with FDC and SDC measured by qRT-PCR. The miR-342-5p level was higher in plasma of patients with SDC than those with FDC (p=0.049).
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
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
Gerard Piñol-Ripoll
Hospital Universitari Santa Maria
Corresponding Author
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 16 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.
Methods: To discover the miRNAs related to the rate of cognitive impairment, we analysed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after two years (<4 points (N=11) and ≥ 4 points (N=8)). The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N=53) with mild AD using RT-qPCR.
Results: In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r=-0.28; p=0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after two years (p=0.049).
Conclusion: Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after two years of follow-up.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- Table1.xlsx
Table 1. Characteristics of the study population that participated in the discovery and validation cohorts. SDC: Slow decline in cognition; FDC: Fast decline in cognition; MMSE: Mini-Mental State Examination; Aβ42: Amyloid beta 42; T-tau: Total tau protein; P-tau: Phosphorylated tau protein
- Supplementarydata.docx
Supplementary Figure 1. Quality control of TaqMan Low Density Array (TLDA) determinations. Number of determinations/missings. Supplementary Figure 2. Ct distribution of miRNAs in TLDA cards. Supplementary Figure 3. The expression stability of the selected endogenous controls characterized by means of GeNorm and Bestkeeper. Supplementary Table 1. miRNAs expressed differentially between FDC and SDC groups in the discovery cohort. Supplementary Figure 4. Ct distribution of miRNAs in RT-qPCR cohort. Supplementary Figure 5. Box plot diagram of the relative expression of miR-342-5p among AD patients with FDC and SDC measured by qRT-PCR. The miR-342-5p level was higher in plasma of patients with SDC than those with FDC (p=0.049).
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