Abstract
Aims: Post-transcriptional regulation has been implicated in Alzheimer’s disease (AD) pathogenesis. Micro RNAs (miRNAs) are post-transcriptional regulators that are highly expressed in brain tissue. Still, previous studies have been limited in both the number of samples and/or the number of molecules assayed to reliably assess the potential involvement of miRNAs in AD. To this end, we compared miRNA expression using RNA sequencing in brain tissue extracted from 174 AD patients and aged control individuals. Methods: Entorhinal cortex (EC) samples were collected from 90 AD patients (61 to 95 years) and 84 healthy controls (41 to 100 years). Total RNA was extracted and small-RNA-sequencing libraries prepared and sequenced at ~2.3M reads/sample on average. MiRNAs were quantified using miRDeep2 and compared between cases and controls using DESeq2, adjusting for potential confounding factors. Additionally generalized linear models were fit to identify miRNAs differentially expressed with respect to Braak-staging. Results: We detected > 600 miRNAs expressed in EC, about one third of which had been previously assessed by the ROS/MAP project (Patrick et al. 2017). For the majority of those, miRNA expression levels show a high correlation (r = 0.698, p-value < 2.2e-16). Leveraging our entire data set, we found > 20 miRNAs significantly differentially expressed between AD cases and controls and over twice as many associated with Braak staging While several differentially expressed miRNAs were already previously reported (e.g. miR-129-3p and miR-195-5p) our study highlights numerous novel miRNAs not previously linked to AD. Conclusions: Our study provides the largest differential miRNA-expression analysis in terms of miRNAs assayed and one of the largest in terms of sample size. Mapping the target mRNAs of these miRNAs holds promise in leading to a better understanding of AD pathogenesis.
Just weeks after moving from LIGA to the Plass lab, I was united with my former colleagues in Gothenburg to present the work had been doing together at AD/PD™ 2023.
The conference was massive, so scheduling was complicated but I got a lot of great input and most importantly a reat overview over what has been happening in the field outside of my own little bubble. I also got to meet long-time collaborators from the UK and the US for the first time in person and made some new connections with people from/in Barcelona. My poster presentation generated a good amount of interest, especially given the huge number of posters and the little time to see them all in-between the parallel sessions.
Besides the scientific part, I/we also had a great time exploring the city of Gothenburg and socializing over sports, food, drinks, and music. A non-professional personal highlight for me was the opportunity to see a Swedish Melodic Death Metal band perform live in Gothenburg, even though none of Gothenburg’s own big names performed while I was there, a ’little band’ from Helsingborg came to town instead.
While I don’t see myself attending one of these massive conferences every year, I will try my best not to let another ten years pass before catching up with the field this way (like I did between 2013’s AAIC and this one).