Observations of extensive gene expression differences in the cerebellum and potential relevance to Alzheimer's disease

Abstract

Objectives: In order to determine how gene expression is altered in disease it is of fundamental importance that the global distribution of gene expression levels across the disease-free brain are understood and how differences between tissue types might inform tissue choice for investigation of altered expression in disease state. The aim of this pilot project was to use RNA-sequencing to investigate gene expression differences between five general areas of post-mortem human brain (frontal, temporal, occipital, parietal and cerebellum), and in particular changes in gene expression in the cerebellum compared to cortex regions for genes relevant to Alzheimer's disease, as the cerebellum is largely preserved from disease pathology and could be an area of interest for neuroprotective pathways.

Results: General gene expression profiles were found to be similar between cortical regions of the brain, however the cerebellum presented a distinct expression profile. Focused exploration of gene expression for genes associated with Alzheimer's disease suggest that those involved in the immunity pathway show little expression in the brain. Furthermore some Alzheimer's disease associated genes display significantly different expression in the cerebellum compared with other brain regions, which might indicate potential neuroprotective measures.

Keywords: Alzheimer’s disease; Cerebellum; Human brain; RNA-sequence.

Fig. 1

Graphic showing the mapping of key associated Alzheimer’s disease genes mapped on to pathways and their relative gene expression determined by RNA-sequencing RPKMs [8]. Genes involved in Cholesterol Metabolism and Endocytosis pathways are highly expressed in the brain, whilst genes involved in Immunity pathways show little expression in the brain (Figure Adapted from Medway and Morgan 2014)