Premium
Performance of validated microRNA biomarkers for Alzheimer’s disease in mild cognitive impairment
Author(s) -
Saugstad Julie A
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047220
Subject(s) - microrna , biomarker , apolipoprotein e , medicine , oncology , area under the curve , cognitive impairment , correlation , diagnostic biomarker , disease , alzheimer's disease , bioinformatics , biology , diagnostic accuracy , genetics , gene , geometry , mathematics
Background Cerebrospinal fluid (CSF) microRNA (miRNA) biomarkers of Alzheimer’s Disease (AD) have been identified, but have not been evaluated in prodromal AD, including Mild Cognitive Impairment (MCI). Here we evaluated the expression of our previously validated CSF miRNA biomarkers for AD in MCI. Method We measured the expression of 17 validated miRNA biomarkers for AD in CSF samples from AD, MCI, and cognitively unimpaired controls. We then examined classification performance of the miRNAs individually and in combination. For each miRNA, we assessed median expression in each diagnostic group and classified markers as trending linearly, nonlinearly, or lacking any trend across the three groups. For trending miRNAs, we assessed multimarker classification performance alone and in combination with apolipoprotein E ɛ4 allele ( APOE ɛ4) genotype and amyloid‐β 42 to total tau ratio (Aβ 42 :T‐Tau). We identified predicted targets of trending miRNAs using pathway analysis. Result Five miRNAs showed a linear trend of decreasing median expression across the ordered diagnoses (control to MCI to AD). The trending miRNAs jointly predicted AD with area under the curve (AUC) of 0.770, and MCI with AUC of 0.705. Aβ42:T‐Tau alone predicted MCI with AUC of 0.758 and the AUC improved to 0.813 (p = 0.051) after adding the trending miRNAs. Multivariate correlation of the five trending miRNAs with Aβ42:T‐Tau was weak. Conclusion Selected miRNAs combined with Aβ 42 :T‐Tau improved classification performance (relative to protein biomarkers alone) for MCI, despite weak correlation with Aβ 42 :T‐Tau. Together these data suggest that that these miRNAs carry novel information relevant to AD, even at the MCI stage. Preliminary target prediction analysis suggests novel roles for these biomarkers.