Figure 5.

Schematic depiction of three separate hypotheses related to brain miRNA expression that could help explain differences in vulnerability to neurodegenerative diseases that are at least partially sex-specific and region-specific. HYPOTHESIS 1: the combination of underlying pathogenic mechanisms and the pathologic phenotype alter the neurochemical milieu and result in a condition-specific miRNA profile. The current study did not find support for this hypothesis with the caveat that the sample sizes were relatively small and thus statistically underpowered to correlate subtle variations in miRNA expression patterns with various pathologic and demographic parameters. HYPOTHESIS 2: there are sex-specific miRNA expression patterns that help to explain the differential vulnerability of males and females to subtypes of neurodegenerative diseases. The current study did not find evidence of robust sex-specific miRNA expression patterns in the sampled brain regions. HYPOTHESIS 3: there are neuroanatomic area-specific patterns of miRNA expression that may help cause those brain regions to have region-specific vulnerability to pathologic phenotypes. Since there were robust differences detected in miRNA patterns across brain regions, including among miRNAs that are hypothesized to target disease-relevant transcripts, we interpret the data from the current study to be compatible with this hypothesis.