ROC analysis indicated that measurement of miR-132-3p in neurally-derived plasma EVs showed good sensitivity and specificity to diagnose AD, but did not effectively separate individuals with AD-MCI from controls.
Moreover, analyzing the hippocampal, temporal and frontal regions from the same LOAD patients, we identify specific sets of deregulated miRNAs for each region, and we confirm that the miR-132/212 cluster is deregulated in each of these regions in LOAD patients, consistent with these miRNAs playing a role in AD pathogenesis.
Correlations of SIRT1, miR-132 and miR-212 expression with cognitive scores were observed for AD patient-derived LCLs and postmortem AD olfactory bulb and hippocampus tissues, suggesting that higher SIRT1 expression, possibly mediated by lower miR-132 and miR-212, may protect aged individuals from dementia and is reflected in their peripheral tissues.
This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.
The dysregulation of miR-132 results in the occurrence and exacerbation of neural developmental, degenerative diseases, like Alzheimer's disease, Parkinson's disease and epilepsy, neural infection and psychiatric disorders including disturbance of consciousness, cognition and memory, depression and schizophrenia.
In this review, we explore the role of three microRNAs, namely miR-132, miR-124 and miR-34, which are dysregulated in major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease.
Our findings indicate that downregulation of miR-132/212 disturbs the balance of S-nitrosylation and induces tau phosphorylation in a NOS1-dependent way, and thereby may contribute to the pathogenesis of AD and other tauopathies.
Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis.
We confirm downregulation of miR-132 and upregulation of ITPKB in three distinct human AD patient cohorts, indicating the pathological relevance of this pathway in AD.
Overall, our results support the hypothesis that the miR-132/212 network, including Sirt1 and likely other target genes, contributes to abnormal Aβ metabolism and senile plaque deposition in AD.
Our findings suggest that mir-132, which has been found to be regulated in three of the here included studies, as well as miRNAs with an already established role in Alzheimer's disease (AD) seem to be particularly promising candidates for future miRNA studies in PTSD.
MiR-132 is enriched in the central nerve system and is thought to be involved in neuronal development, maturation and function, and to be associated with several neurological disorders including Alzheimer's disease.
In agreement with this idea, we provide independent cohort validation for changes in miR-132 expression levels in AD (n = 8) and FTLD (n = 14) cases when compared to controls (n = 8).