MicroRNAs (
miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of
miRNAs in
neurodegenerative diseases (
NDs) have focused on individual diseases such as
Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using
RNA deep sequencing, we sought to analyze in detail the small RNAs (including
miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5),
dementia with Lewy bodies (n = 4),
hippocampal sclerosis of aging (n = 4), and frontotemporal lobar
dementia (
FTLD) (n = 5) cases, together accounting for the most prevalent ND subtypes. All cases had short postmortem intervals, relatively high-quality
RNA, and state-of-the-art neuropathological diagnoses. The resulting data (over 113 million reads in total, averaging 5.6 million reads per sample) and secondary expression analyses constitute an unprecedented look into the human cerebral cortical miRNome at a
nucleotide resolution. While we find no apparent changes in isomiR or
miRNA editing patterns in correlation with ND pathology, our results validate and extend previous
miRNA profiling studies with regard to quantitative changes in
NDs. 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). The identification of common and ND-specific putative novel brain
miRNAs and/or short-hairpin molecules is also presented. The challenge now is to better understand the impact of these and other alterations on neuronal gene expression networks and neuropathologies.