Katie Lunnon (United Kingdom)
University of Exeter
College of Medicine and Health
Katie Lunnon is a Professor of Dementia Genomics at the University of Exeter. She leads a research group focussed on investigating mechanisms of genomic regulation in diseases characterized by dementia. She currently holds >£3 million as PI and currently is funded by the NIH, MRC and various National and international charities. She has authored 80 publications and has recently led the first cross tissue meta-analysis of epigenomics in Alzheimer’s disease, which was published in 2020. Her team currently consists of five postdoctoral research fellows, one graduate research associate and eight PhD students (five as first supervisor). Her team are exploring and integrating genetic, epigenetic and transcriptomic datasets from brain and blood in a range of different neurodegenerative diseases to identify new disease mechanisms, biomarkers and treatments.

Moderator of 1 Session

 Conference Calendar
SYMPOSIUM

NEUROPATHOLOGY IN AD, LBD AND OTHER DEMENTIA 2

Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:30 PM
Room
ONSITE: 133-134
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

TAU PATHOLOGY-ASSOCIATED ALTERATIONS IN MICRORNAS IN ALZHEIMER’S DISEASE ENTORHINAL CORTEX

Session Name
0780 - NEUROPATHOLOGY IN AD, LBD AND OTHER DEMENTIA 2 (ID 134)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:30 PM
Room
ONSITE: 133-134
Lecture Time
03:00 PM - 03:15 PM
Presenter

Abstract

Aims

In the present study we performed high-throughput small RNA sequencing in post-mortem entorhinal cortex brain tissue from 85 individuals with either low (Braak 0-II) or high (Braak V-VI) levels of neurofibrillary tangle pathology, with the aim of identifying differentially expressed microRNAs (miRNAs) associated with Alzheimer’s disease.

Methods

We quantified the expression of 490 highly expressed miRNAs, utilizing weighted gene correlation network analysis (WGCNA) to identify co-expressed miRNAs. Subsequently we performed in silico identification of miRNA-regulated protein-protein interaction (PPI) networks to determine potential downstream dysregulated pathways that result from these tau-associated miRNA alterations.

Results

We identified 49 nominally-significant miRNAs, of which 28 were upregulated and 21 were downregulated. Of these, two of the down-regulated miRNAs passed the Bonferroni threshold for multiple testing correction: miR-212-3p and miR-132-3p. Using WGCNA we identified 14 co-ecpressed miRNA modules, with one being significantly associated with pathology, and containing 17 miRNAs, including miR-212-3p and miR-132-3p. To explore the miRNA regulation of PPI networks in AD we identified the mRNA targets of the 49 nominally-significant Braak-associated miRNAs, showing enrichment for ubiquitin-related pathways.

Conclusions

Alterations in miRNA expression levels have been previously reported in AD in multiple brain regions, blood and CSF. However, the use of different tissue types, small sample sixes and various different assay techniques has resulted in inconsistent findings to date. We have quantified genome-wide miRNA expression levels in post-mortem entorhinal cortex and found down-regulation of miR-212-3p and miR-132-3p after Bonferroni adjustment for multiple testing. Pathway analysis highlighted that mRNAs targeted by the nominally-significant miRNAs, were enriched in ubiquitin-related pathways.

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