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Objectives

The deposition of tau protein aggregates in the brains of affected individuals has a critical role in Alzheimer's disease (AD). In this project, we use Drosophila as a model organism to identify the molecular mechanisms that cause Alzheimer's disease and associated tauopathies. We hypothesize that 1) deregulation of RNA expression, 2) specific transposable elements, and 3) associated piRNAs, small RNAs that silence transposable elements, mediate tau-induced neurotoxicity. We validate our findings from RNA-sequencing by RT-PCR and Nanostring, and perform comparative analyses in postmortem human brain.

Data

  1. Whole RNA-seq on 3 control and 3 tau transgenic samples. Each sample is composed of heads of 6 male and 6 female flies, all 10 days old.
  2. Small RNA sequencing on the same above samples.
  3. Human RNA-Seq data from Mayo Clinic to test these hypotheses, which Bess made based on Drosophila data. Specifically, the raw fastq files from MayoRNAseq dataset for NCI, PSP, AD, and PA (Synapse ID: syn5550404, cerebellum and temporal cortex).
  4. Human RNA-seq data from iPSC-derived neurons from 3 patients with tauopathy, along with 3 CRISPR-corrected isogenic control samples. On 24 April 2018, Celeste Karch provided us with bam files of the data from their JAMA Neurology 2018 paper (readme.txt).
  5. Single-cell sequencing data (GSE107451) of Drosophila brain in 2 age groups with a median of 53K reads from 57K cells. They identified 87-151 cell types.