This project aims to validate multicomponent biosignatures for neurodegenerative and psychiatric diseases, such as Alzheimer’s disease (AD) and Major Depressive Disorder (MDD), to enable subtyping of patients to match them with appropriate therapies and track their treatment responses. Researchers have hypothesized that aberrant immune function contributes to, or correlates with, the development and/or progression of a wide range of central nervous system (CNS) disorders, and that measuring inflammatory markers in blood and/or cerebrospinal fluid (CSF) will yield multicomponent biomarkers that will be useful in diagnosing patients and predicting their treatment outcomes. Because no single analyte is likely to define reliable patient endophenotypes, it is necessary to develop a core panel of inflammation-related analytes to define specific biomarker signatures. Furthermore, lack of consensus and conflicting results surrounding inflammation biomarkers in CNS literature stems largely from small sample sizes, and insufficiently sensitive assay technologies. Additionally, the Research to date shows a lack of technical assay validation and panel standardization, with many differences in collection, handling and storage conditions for human samples.
Using technically validated and modern, highly sensitive assays for biomarker quantification, as well as appropriately powered and harmonized sample collection and handling procedures across sites where human samples are obtained, this two-year Biomarkers Consortium project aims to identify and validate plasma and/or CSF-based multicomponent inflammatory biosignatures in AD and MDD, which will aid in the diagnosis and subtyping of patients with these conditions. Furthermore, the information generated by these efforts will help to inform development of novel therapeutics and may facilitate clinical studies in which patients would be enrolled, at least in part, based on their biosignatures
- Alzheimer’s Drug Discovery Foundation*
- Biogen MA Inc.*
- Boehringer Ingelheim*
- Genentech, a member of the Roche Group*
- Janssen Research & Development, LLC*
- Regeneron Pharmaceuticals Inc.*
*Provided financial or in-kind support for this program.
- Methods Development and Assay Validation. (a) Identify analytes for inclusion in a broad panel of standard inflammation markers to be evaluated in human plasma and CSF. (b) Assemble a set of samples from existing sources of AD and MDD patients and healthy controls to support assay validation. (c) Select and technically validate the assay platform(s) of interest.
- Biosignature Development. (a) Assemble a well-characterized sample set from existing sources from AD and MDD patients and healthy controls (training set). (b) Accurately measure the levels of inflammatory markers in CSF and plasma in the training set. (c) Identify correlations of these measurements with each other and with clinical observations (biosignature development).
Results & Accomplishments
The project team has technically validated all of the assays and is awaiting a donation of samples to meet the first milestone of the project. For the Biosignature Development, the project team has identified the MDD and AD plasma samples.
FNIH Web Announcement (April 26, 2018): The FNIH Biomarkers Consortium Launches Project to Improve Diagnosis and Treatment of Neurodegenerative and Psychiatric Diseases