An article published in Nature Medicine demonstrates the effectiveness of a large-scale dementia protein database composed of identically formatted and easily combinable data. The Global Neurodegeneration Proteomics Consortium (GNPC) database is a resource for scientists researching FTD and other neurodegenerative diseases to better understand the protein signatures associated with diseases. This shared resource can promote progress in scalable biomarker discovery by eliminating differences in data formats, the data points collected, and restrictions on data access.

AFTD Clinical Research Training Scholarship recipient Rowan Saloner, PhD, and Accelerating Drug Discovery for FTD recipient Jeffery Rothstein, MD, PhD, are among the co-authors of the study. The Clinical Research Training Scholarship is made possible thanks to the support of the Holloway Family Fund, with additional support from the American Brain Foundation in collaboration with the American Academy of Neurology. Accelerating Drug Discovery for FTD is supported by the partnership of the Alzheimer’s Drug Discovery Foundation and AFTD.

Analysis Reveals Different Protein Levels Across Dementias

This first GNPC study highlighted how their large-scale protein database could address key research questions by conducting different analyses, each providing insight into a specific aspect of FTD and other dementias. This analysis revealed how the levels of thousands of separate proteins varied across dementias and reflected a wide range of pathological changes and dementia features. For example, blood protein signatures have been found to reflect carrier status for a risk gene commonly associated with Alzheimer’s disease.

Notably, a group of proteins was found to correspond with the severity of clinical impairment caused by FTD, Alzheimer’s, and Parkinson’s disease. High levels of the 256-protein group were associated with lower cognitive test scores and a higher Clinical Dementia Rating score, a widely used scale for assessing dementia severity. The strength of the correlation between levels of the protein group and clinical severity varied between dementias, with the strongest correlation in FTD.

In addition to providing novel insights into FTD and other dementias, the study demonstrates the utility of a large-scale protein database. Analyzing large numbers of proteins at once can not only shed light on the underlying mechanisms of dementia but can also make finding targets for potential drugs much easier. Large-scale databases can also help scientists refine protein biomarker detection methods, paving the path towards more accessible diagnostic tools such as blood tests.

International Public and Private Cooperation Helped Build the Protein Data Bank

As the authors emphasize, scientists face several challenges when attempting large-scale data analysis. Some obstacles include the varied data-sharing rules of different countries and the differing priorities of research and industry organizations. The GNPC aims to address these challenges to aid biomarker and drug development and further our understanding of the underlying mechanisms of dementias, such as FTD.

To do so, 23 partner organizations within the GNPC, which include studies such as ALLFTD and institutions like the Mayo Clinic, contributed data from 18,645 people with FTD, ALS, Alzheimer’s, or Parkinson’s who visited GNPC clinics. The protein data were combined with demographic and clinical data collected at each visit.

However, data points measuring the same thing are not always the same, as clinicians and researchers often record their findings differently. GNPC, however, worked to harmonize the measurements they received, ensuring that related data points (such as measurements of a specific protein in cerebrospinal fluid across different people) are formatted similarly and complement each other. Harmonized datasets are important for larger-scale studies, as researchers can easily find larger amounts of data that meet their needs.

The FTD Disorders Registry: A Powerful Tool for FTD Research

Large-scale databases and disorder registries are powerful tools for researchers to better understand dementias like FTD. Sign up at the FTD Disorders Registry to learn about recruiting studies that match your interests. You may also be eligible for the online Registry Research Study to share insights about diagnosis, family history, lived experience, genetic testing, medical records, and more. Numbers have power. The more participants, the closer we come to a future free of FTD.