Project description:Gene expression profiling was performed on frontal and temporal cortex from vascular dementia (VaD), Alzheimer's disease (AD), and non-demented controls (Control) obtained from the University of Michigan Brain Bank. Controls and AD cases had no infarcts in the autopsied hemisphere. Vascular dementia cases had low Braak staging.
Project description: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 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 single 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. 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.
Project description:Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia but their pathology may involve the same cortical areas with overlapping cognitive manifestation. Dementia cases within the same family share a common genetic background. Nonetheless, the clinical phenotype may be different due to the different underlying molecular processes that come-up apart from genetics, causing diverse neurodegeneration. Through neuropathological, genetic and transcriptomic comparison of four different brain areas (substantia nigra, hippocampus, parietal lobe and basal ganglia), we defined commonalities and differences in the pathological processes of dementia in two kindred cases, a mother and a son, who developed a classical AD and an aggressive form of AD/LBD respectively. Genetic analysis did not reveal any pathogenic variants in the principal AD/LBD-causative genes. RNA sequencing highlighted high transcriptional dysregulation within the substantia nigra in LBD pathology, while AD underwent lower degree of transcriptional dysregulation, with the parietal lobe being the most involved brain area. Conversely, hippocampus (the most degenerated area) and basal ganglia (lacking specific lesions) expressed the lowest level of dysregulation. Our data suggest that there is a link between the transcriptional dysregulation and the amount of tissue damage accumulated across time, assessed through neuropathology. Moreover, we highlight that the molecular bases of AD and LBD follow very different pathways, which underlie their neuropathological signatures. Indeed, the transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological analysis for a deeper understanding of AD and LBD pathogenesis.
Project description:Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated multi-omics datasets for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. This experiment contains data from smRNA-sequencing of human post-mortem brain tissue of the frontal lobe from patients with FTD caused by mutations in GRN, MAPT or C9orf72 and healthy controls.
Project description:Single-nucleus RNA sequencing of human periventricular white matter comparing healthy age-matched controls with vascular dementia patients.
Project description:We used the Illumina 450KMethylation BeadChip to measure DNA methylation at 485,512 loci across the genome for 40 postmortem brain samples. The purpose of our study was to identify differentially methylated regions (DMRs) associated with autism. Samples included 16 temporal cortex brain tissue samples (6 cases and 10 controls), 11 prefrontal cortex brain tissue samples (6 cases and 5 controls), and 13 cerebellum brain tissue samples (7 cases and 6 controls).
Project description: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 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 single 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.