Inflammation-related miR-155-5p as an APOE ε4-modulated biomarker for amyloid pathology in mild cognitive impairment
Kohsuke Yoshida1,2, Nonoka Saito3, Ryuichi Takahashi2
1Department of Public Health, Kobe University Graduate School of Health Sciences, Suma, Kobe, Japan.
Abstract:
BackgroundAlzheimer's disease (AD), the most common neurodegenerative cause of dementia, is defined by amyloid-β (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau, while inflammatory processes are increasingly recognized as contributors to its pathogenesis. However, the clinical relevance of inflammation-related microRNAs (miRNAs) in AD remains unclear.ObjectiveTo evaluate whether inflammation-related miRNAs in plasma and cerebrospinal fluid (CSF) are associated with AD pathology and apolipoprotein E (APOE) ε4 status in individuals with mild cognitive impairment (MCI).MethodsWe investigated the expression of inflammation-related miR-125b, miR-146a, and miR-155-5p in plasma and CSF of individuals with MCI (N = 103), stratified by APOE ε4 status. Associations with established CSF biomarkers of AD pathology were assessed. In a subset receiving the anti-Aβ antibody lecanemab (N = 18), longitudinal changes in plasma inflammation-related microRNA levels were evaluated.ResultsPlasma miR-155-5p levels in APOE ε4 non-carriers were associated with the CSF Aβ42/40 ratio, whereas in ε4 carriers, CSF miR-155-5p levels correlated with phosphorylated tau 181 and total tau. miR-155-5p was the only inflammation-related miRNA showing consistent APOE ε4-dependent differential expression in both plasma and CSF. In the lecanemab-treated subset, plasma miR-155-5p increased significantly after 6 months and remained elevated at 12 months.ConclusionsmiR-155-5p, an inflammation-related miRNA modulated by APOE ε4, is associated with AD-relevant pathological features and may provide complementary information at the MCI stage, with potential utility in monitoring biological responses to anti-Aβ therapy.
Insights
Alzheimer's disease (AD) research shows inflammation-related microRNA miR-155-5p is linked to AD pathology and apolipoprotein E (APOE) ε4 status in mild cognitive impairment (MCI). This miRNA may help monitor treatment response.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-β plaques and tau tangles, with inflammation increasingly recognized as a key factor.
- The role of inflammation-related microRNAs (miRNAs) in AD pathogenesis and their clinical significance, particularly in early stages like mild cognitive impairment (MCI), remain unclear.
Purpose of the Study:
- To investigate the association between inflammation-related miRNAs (miR-125b, miR-146a, miR-155-5p) in plasma and cerebrospinal fluid (CSF) with AD pathology and apolipoprotein E (APOE) ε4 status in individuals with MCI.
- To explore the potential of these miRNAs as biomarkers for AD and their response to anti-amyloid-beta (Aβ) therapy.
Main Methods:
- Expression analysis of miR-125b, miR-146a, and miR-155-5p in plasma and CSF of 103 MCI patients, stratified by APOE ε4 status.
- Correlation analysis with established CSF biomarkers of AD pathology (Aβ42/40 ratio, phosphorylated tau 181, total tau).
- Longitudinal evaluation of plasma miR-155-5p levels in a subset of 18 patients treated with the anti-Aβ antibody lecanemab.
Main Results:
- Plasma miR-155-5p levels correlated with the CSF Aβ42/40 ratio in APOE ε4 non-carriers.
- In APOE ε4 carriers, CSF miR-155-5p levels correlated with phosphorylated tau 181 and total tau.
- miR-155-5p was the sole inflammation-related miRNA exhibiting consistent APOE ε4-dependent differential expression in both plasma and CSF.
- Plasma miR-155-5p levels significantly increased after 6 months of lecanemab treatment and remained elevated at 12 months.
Conclusions:
- miR-155-5p, an inflammation-related miRNA influenced by APOE ε4 status, is associated with AD-relevant pathological features in MCI.
- This miRNA may offer complementary diagnostic information at the MCI stage.
- miR-155-5p shows potential utility in monitoring biological responses to anti-Aβ therapies like lecanemab.
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