Gene expression profiling of brain samples from patients with Lewy body dementia

Abstract

Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative disorder in the elderly. The development and progression of DLB remain unclear. In this study we used next generation sequencing to assess RNA expression profiles and cellular processes associated with DLB in the anterior cingulate cortex, a brain region affected by DLB pathology. The expression measurements were made in autopsy brain tissues from 8 DLB subjects and 10 age-matched controls using AmpliSeq technology with ion torrent sequencing. The analysis of RNA expression profiles revealed 490 differentially expressed genes, among which 367 genes were down-regulated and 123 were up-regulated. Functional enrichment analysis of genes differentially expressed in DLB indicated downregulation of genes associated with myelination, neurogenesis, and regulation of nervous system development. miRNA binding sites enriched in these mRNAs yielded a list of candidate miRNAs participating in DLB pathophysiology. Our study provides a comprehensive picture of gene expression landscape in DLB, identifying key cellular processes associated with DLB pathology.

Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

“…Notably, these findings occurred in a region that typically manifests relatively mild α‐synuclein deposition yet is postulated to play a central role in the cognitive profile of DLB. The reported changes differ markedly from a previous study that employed RNA‐seq in the cingulate gyrus, a region with more severe α‐synuclein pathology, and that reported genes involved in neurogenesis and myelination enriched in DLB cases when compared with controls …”

“…The reported findings are within a region with relatively low levels of Lewy body pathology and differ from those reported in a more severely affected region, the cingulate gyrus . These findings indicate important molecular changes, in addition to previously reported neuronal loss, independent of the severity of local neuropathological changes.…”

“…The reported findings are within a region with relatively low levels of Lewy body pathology and differ from those reported in a more severely affected region, the cingulate gyrus. 37 These findings indicate important molecular changes, in addition to previously reported neuronal loss, 21 independent of the severity of local neuropathological changes. Although we noted a relationship between tau pathology in the pulvinar and the frequency and severity of visual hallucinations intra vitam, the overall levels of tau were very low in the pulvinar in DLB.…”

“…The reported changes differ markedly from a previous study that employed RNA-seq in the cingulate gyrus, a region with more severe a-synuclein pathology, 2 and that reported genes involved in neurogenesis and myelination enriched in DLB cases when compared with controls. 37 The reported synaptic changes indicate lower expression levels of presynaptic proteins such as synaptophysin and NSF, which support efficient turnover of vesicles following exocytotic events. 38 In contrast, we found the preservation of proteins necessary for vesicular exocytosis, such as SNAP25, 39 STX1A, 40 and SV2B.…”

Systematic review of genetic association studies in people with Lewy body dementia

“…Meanwhile, there is a need for more hypothesis‐driven studies for replicating reported genetic associations of LBD and for exploring their functional implications. Gene expression studies and transcriptomic analyses of post‐mortem LBD brains or of circulating exosomes of people living with LBD may help understanding the functional significance of the genetic associations and their molecular networks . Future hypothesis‐driven studies should prioritise the identified genetic associations of LBD that do not overlap with known AD risk genes.…”