Transcriptome analysis of zebrafish models of familial Alzheimer's disease and Sanfilippo syndrome childhood dementia display effects-in-common on the lysosome, oxidative phosphorylation and the ribosome

Here, we use intra-family analysis to compare the gene expression profiles of one of our zebrafish models of EOfAD; psen1Q96_K97del) and our model of Sanfilippo syndrome (MPS IIIB, nagluA603fs ) in young adult brains (6 months of age). We identified distinct changes to gene expression in each model at both ages. However, important commonalities were also observed, pointing to fundamental, underlying similarities in pathological mechanisms. Our findings highlight the potential of zebrafish models as valuable tools for investigation of neurodegenerative diseases. We crossed a psen1Q96_K97del/+ ; nagluA603fs/+ zebrafish with a psen +/+ ; nagluA603fs/+ zebrafish, to generate a family of 100 sibling zebrafish with a number of various genotypes. We raised the entire family of fish until 6 months of age in shared environments (4 tanks side-by-side in the same recirculating water system). Then, the entire was euthanised by cold water shock. Each fish was genotyped, then n = 8 fish per wild type, EOfAD-like (psen1 Q96_K97del heterozygous) and MPS IIIB (naglu A603fs homozygous) genotype were selected for RNAseq of their brain RNA