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MRI scan of brain in patient with Alzheimer's disease

Protein expression changes in human brain with Alzheimer’s disease

Measuring changes in protein level in the human Alzheimer’s brain shows regional differences and reveals new information about the disease.

Protein expression changes in human brain with Alzheimer’s disease

Full title

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

 

Journal

Communications Biology

 

Authors

Jingshu Xu, Stefano Patassini, Nitin Rustogi, Isabel Riba-Garcia, Benjamin D. Hale, Alexander M Phillips, Henry Waldvogel, Robert Haines, Phil Bradbury, Adam Stevens, Richard L. M. Faull, Andrew W. Dowsey, Garth J. S. Cooper & Richard D. Unwin.

 

Measuring changes in protein level in the human Alzheimer’s brain shows regional differences and reveals new information about the disease.

Alzheimer’s disease (AD), the leading cause of dementia, remains the only one of the top 10 causes of death to have no treatments which slow or halt the disease. New information regarding how the disease develops, and generating targets for new drugs, is essential.

Here, we collected brain tissue from people with (AD) and age-matched non-AD controls, isolated several distinct regions of the brain, then applied mass spectrometry to measure the levels of 5,000 proteins in each sample, allowing us to compare changes in AD across distinct regions.

These data produced several key findings. Firstly we detected a gradient of changes through the different regions; those affected later in disease show a pattern of change which represents the initial stages of damage, where treatment is most likely to be successful.

We also noted that cerebellum, thought to be unaffected in AD, demonstrates a unique pattern of changes which appears to actively protect this region. We also identified several metabolic and signalling pathways as being altered in AD for the first time; these represent new targets for drug development.

This dataset contains a large amount of valuable information, so we have made all of our data available via a searchable web page.

Key facts

  • We urgently need a better understanding of the processes which underpin Alzheimer’s disease.
  • Our analysis shows a gradient of protein changes, which follows disease spread through the brain.
  • Cerebellum, thought to be unaffected by AD, displays a protective programme of expression changes.
  • Data regarding the protein levels of around 5,000 proteins in up to six brain regions can be found at: Explore the Alzheimer’s Disease Proteome.

Contributing authors

 

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Footnotes

Funded by Alzheimer’s Research UK.