Regional protein expression in human Alzheimer’s brain correlates with disease severity

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions display varying and region-specific changes in protein expression. These changes provide insights into the progression of disease, novel AD-related pathways, the presence of a gradient of protein expression change from less to more affected regions and a possibly protective protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and open new avenues to enhance molecular understanding of AD pathophysiology, provide new targets for intervention and broaden the conceptual frameworks for future AD research. Jingshu Xu et al. did a comprehensive post-mortem proteomics analysis across six brain regions obtained from Alzheimer’s disease patients and controls. With this spatial proteomics approach, they identified new disease-related pathways and a gradient of protein expression changes that correlates with the pathology of the affected regions.