A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

Abstract

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.

Glutamatergic Synapse Dysfunction in Drosophila Neuromuscular Junctions Can Be Rescued by Proteostasis Modulation

“…These results suggest higher male susceptibility toward Q78 pathology. This result is in line with available literature in humans, which report gender bias in the progression of many neurodegenerative conditions (Hanamsagar and Bilbo, 2016;Piscopo et al, 2021). We also observed wing defects in eclosed flies on the expression of Q78 protein.…”

Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study

“…Although we analyzed repeated measures of cognitive function, this study is limited to a single plasma miRNA measure, and thus it is unknown how the abundance of these circulating miRNAs may fluctuate over time. Lastly, these results are based on a cohort of older, mostly white men and may be generalizable only to populations with similar characteristics [ 50 ]. However, the results of our KEGG enrichment analyses are in close agreement with another study that examined the plasma EV-miRNA profile of patients with AD that were mostly female (4 out of 5) and healthy controls that were younger and contained an equal balance of males and females [ 45 ].…”

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

“…The current study shows that the occurrence of PD is different in gender, and it is also correlated with the onset age to a certain extent. Previous studies have shown that miRNAs, which can be used as plasma markers, are also gender-dependent in the expression of PD ( Piscopo et al, 2021 ). The biological significance of this sex association has not been clarified, but an increase in the prevalence of PD in men has been recognized.…”