Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1–40 and cerebral vulnerability in normal aging

BACKGROUND: Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β (Aβ) deposition and chronic cerebral hypoperfusion, both factors largely associated with the development of AD. Moreover, reduced 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of AD. Based on this evidence, we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly subjects. METHODS: Ninety-five normal elderly subjects underwent clinical, cognitive, structural MRI, and FDG-PET explorations. Serum expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this cohort. Regression analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning, plasma Aβ, structural and metabolic brain changes. RESULTS: Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ(1–40), deficits in cortical glucose metabolism, and volume reduction of the entorhinal cortex. No significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical thinning. CONCLUSIONS: These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.