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Exosomal MicroRNA-Based Predictive Model for Preclinical Alzheimer's Disease: A Multicenter Study
Longfei Jia1, Min Zhu1, Jianwei Yang1
1Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
Background:
Exosomal microRNAs (miRNAs) have been demonstrated to be biomarkers of Alzheimer's disease (AD). However, whether exosomal miRNAs can predict AD at the asymptomatic stage remains unclear.
Methods:
This study is a multicenter study with four independent datasets to verify the capacity of exosomal miRNAs to identify preclinical AD. Subjects were recruited from a Beijing center in the pilot study (dataset 1: subjects with AD, n = 20; control subjects, n = 20), from other centers across China (dataset 2: subjects with AD, n = 95; control subjects, n = 93), a longitudinal cohort (dataset 3: subjects with preclinical AD, n = 101; control subjects, n = 102), and a confirmation study on familial AD (dataset 4: mutation carriers, n = 56; nonmutation carriers, n = 57).
Results:
A panel of miRNAs was changed in subjects with AD and can detect preclinical AD 5 to 7 years before the onset of cognitive impairment (areas under the curve = 0.85-0.88).
Conclusions:
Exosomal miRNAs can be effective biomarkers for predicting AD 5 to 7 years prior to cognitive impairment onset.
Insights
Exosomal microRNAs (miRNAs) show promise for early Alzheimer's disease (AD) detection. These biomarkers can identify preclinical AD 5-7 years before cognitive symptoms appear, aiding in early intervention strategies.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Genomics
Background:
- Exosomal microRNAs (miRNAs) are recognized biomarkers for Alzheimer's disease (AD).
- The predictive capacity of exosomal miRNAs for asymptomatic or preclinical AD remains largely uninvestigated.
Purpose of the Study:
- To validate the efficacy of exosomal miRNAs in identifying Alzheimer's disease (AD) during its preclinical stages.
- To assess the potential of exosomal miRNAs as early diagnostic markers for AD.
Main Methods:
- A multicenter study utilizing four independent datasets.
- Inclusion of diverse cohorts: pilot AD vs. control, larger Chinese cohort, longitudinal preclinical AD cohort, and familial AD cohort.
- Analysis of exosomal miRNA panels for diagnostic accuracy.
Main Results:
- A specific panel of exosomal miRNAs demonstrated altered levels in subjects with AD.
- This miRNA panel accurately identified preclinical AD 5 to 7 years before the onset of cognitive impairment.
- High diagnostic accuracy was achieved, with areas under the curve ranging from 0.85 to 0.88.
Conclusions:
- Exosomal miRNAs are effective biomarkers for predicting Alzheimer's disease.
- Early detection of preclinical AD is feasible 5-7 years prior to clinical symptom manifestation.
- This finding supports the development of novel diagnostic tools for early AD intervention.
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