No abstract

Evidence has shown that microRNAs (miRNAs) are involved in molecular pathways responsible for aging and prevalent aging-related chronic diseases. However, the lack of research linking circulating levels of miRNAs to changes in the aging brain hampers clinical translation. Here, we have investigated if serum expression of brain-enriched miRNAs that have been proposed as potential biomarkers in Alzheimer’s disease (AD) (miR-9, miR-29b, miR-34a, miR-125b, and miR-146a) are also associated with cognitive functioning and changes of the cerebral cortex in normal elderly subjects. Results revealed that candidate miRNAs were linked to changes in cortical thickness (miR-9, miR-29b, miR-34a, and miR-125b), cortical glucose metabolism (miR-29b, miR-125b, and miR-146a), and cognitive performance (miR-9, miR-34a, and miR-125b). While both miR-29b and miR-125b were related to aging-related structural and metabolic cortical changes, only expression levels of miR-125b were associated with patterns of glucose consumption shown by cortical regions that correlated with executive function. Together, these findings suggest that serum expression of AD-related miRNAs are biologically meaningful in aging and may play a role as biomarkers of cerebral vulnerability in late life.

Tremendous progress has been made over the last few years in understanding how sleep and amyloid-β (Aβ) cooperate to speed up the progression of Alzheimer’s disease (AD). However, it remains unknown whether sleep deficits also interact with other risk factors that exacerbate the pathological cascade of AD. Based on evidence showing that higher levels of homocysteine (HCY) and sleep loss increase oxidative damage, we here investigate whether the relationship between HCY and total antioxidant capacity (TAC) is mediated by changes in objective sleep in healthy older (HO, N = 21) and mild cognitive impairment (MCI, N = 21) subjects. Results revealed that reduced TAC levels in MCI was significantly correlated with increased HCY, shorter sleep duration, lower sleep efficiency, and reduced volume of temporal regions. However, only the HCY-TAC association showed diagnostic value, and this relationship was mediated by poorer sleep quality in MCI patients. We further showed that HCY-related cerebral volume loss in MCI depended on the serial relationship between poorer sleep quality and lower TAC levels. These findings provide novel insights into how impaired sleep may contribute to maintain the relationship between HCY and oxidative stress in prodromal AD, and offer empirical foundations to design therapeutic interventions aimed to weaken this link.