Protein aggregation of DISC1, as assayed by insolubility, varies across the brain of an individual with schizophrenia and Alzheimer’s disease

Abstract

AbstractObjectiveSubgroups of mental illness patients have been seen to display disturbed proteostasis, with specific proteins aggregating in their brain, which is generally determined by assaying protein insolubility in thepost mortemsamples. Such studies typically only look at one region of the brain, and therefore we aimed to determine the distribution of protein across a single brain, using this insolubility-based approach.MethodsWe looked at 20 postmortemtissue samples from across the brain of a single patient, with schizophrenia and Alzheimer’s disease, determined which protein(s) aggregated in his brain relative to controls, based on purification of insoluble protein fractions. The individual samples were then similarly analysed.ResultsDisrupted in Schizophrenia 1 (DISC1) protein was seen to be insoluble in the patient’s brain, however in a very heterogenous picture, with differences in insoluble DISC1 even between samples of the same region, but opposite hemispheres.ConclusionsWhile caution must be taken in extrapolating from a single individual, this raises the possibility that aggregates of DISC1 may spread throughout the brain, as is the case for proteins in neurodegenerative disorders, and suggests that current studies looking at single brain regions may be underestimating the prevalence of protein aggregates in schizophrenia.