Project description:INTRODUCTION: Neuropsychiatric symptoms are common in people with Alzheimer’s disease (AD) across all severity stages. Their heterogeneous presentation and variable temporal association with cognitive decline suggest shared and distinct biological mechanisms. We hypothesized that specific patterns of gene expression associate with distinct NIMH Research Domain Criteria (RDoC) domains in AD. METHODS: Post-mortem bulk RNAseq on the insula and anterior cingulate cortex from 60 brain donors representing the spectrum of canonical AD neuropathology combined with natural language processing approaches based on the RDoC Clinical Domains. RESULTS: Distinct sets of >100 genes (pFDR<0.05) were specifically associated with at least one clinical domain (Cognitive, Social, Negative, Positive, Arousal). In addition, dysregulation of immune response pathways was shared across domains and brain regions. DISCUSSION: Our findings provide evidence for distinct transcriptional profiles associated with RDoC domains suggesting that each dimension is characterized by specific sets of genes providing insight into the underlying mechanisms.
Project description:Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. Post-mortem derived BA10 tissue from 28 schizophrenic and 23 control patients were compared. Age, gender, post-mortem delay and pH of brain lysates data were also captured.
Project description:Epigenome Analysis of Post-Mortem Human Temporal Pole Brain Tissue For more information, please refer to DOI: 10.3233/JAD-141989 Temporal Pole regions from 24 age-matched causcasian males: 8 samples which died of normal causes, 8 samples with Alzheimer's disease (stage 3/4) and 8 samples with dementia with lewy bodies