Neuroimmune proteins can be used as biomarkers in the diagnosis of neurodegenerative diseases

Researchers from the BU CTE Center have found that immune-related proteins can help distinguish neurodegenerative diseases and provide additional candidates for biomarkers or novel therapeutic targets
.

One of the biggest challenges in neuroscience is identifying and treating neurodegenerative diseases during life, as many diseases can only be diagnosed
after death.
In addition, some diseases sometimes have overlapping clinical symptoms that make diagnosis more challenging, including Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and silver-philic particulate disease (AGD), highlighting the need for better ways to identify and distinguish
in life.

"We found that the CCL21 protein is specific for CTE, the FLT3L protein is selective for AD, and the IL-13 protein is the highest
in PSP.
This is novel because it offers more possible biomarkers to help better identify diseases in life, such as CTE, AD, PSP, CBD or AGD
.
In addition, it helps us better understand the mechanisms behind each disease," said corresponding author Jonathan Cherry, Ph.
D.
, a research health scientist at Boston Healthcare System for veterans and assistant professor
of pathology and laboratory medicine at Boston University's Jobanian & Aviddison School of Medicine.

The researchers examined postmortem brain tissue
from 127 patients with CTE, AD, PSP, CBD or AGD.
They analyzed the concentrations of 71 different immune-related proteins and used statistical techniques to determine whether specific protein clusters were most associated
with specific diseases.
After identifying the protein clusters for each disease, they picked the top five proteins in each cluster to determine which protein was the strongest biomarker candidate
.
They then validated the initial results
by comparing postmortem cerebrospinal fluid from CTE and AD patients.

"We demonstrate that the protein CCL21 is able to distinguish CTE and AD in spinal fluid, further underscoring the future as a new biomarker for life diagnosis
.
" An important caveat, however, is that there will most likely not be a single "wonder protein" used to diagnose
any disease.
Eventually, these proteins will need to be combined with several other biomarkers, imaging studies, and clinical symptoms to be truly effective
.
However, here we provide more targets that can help improve the overall specificity of the diagnosis," he added
.

According to the researchers, these results underscore the importance of
the immune system for neurodegenerative diseases.
In addition, they argue, a better understanding of the characteristics of neuroinflammation, which is specific to individual neurodegenerative diseases, could lead to the identification of more specific biomarkers for all diseases and the eventual discovery of new therapeutic compounds
.

The findings were published online
in the Journal of Neuroinflammation.

Funding for this study was provided by the Department of Veterans Affairs Biobank (BX002466), the Department of Veterans Affairs Career Development Award (BX004349), NIA (Boston University AD Center P30AG072978, Mayo AD Research Center P30AG062677, F31NS127449), NINDS (U54NS115266), and NIH (R01AG062348).