Neuroimmune proteins can differentiate between tauopathies.

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Tauopathies, including Alzheimer's disease (AD), are neurodegenerative diseases characterized by abnormal tau protein accumulation.
• Distinct molecular drivers and biomarkers for differentiating tauopathies remain elusive.
• Neuroinflammation is increasingly recognized as a potential factor specific to different tauopathies.

Purpose of the Study:

• To investigate distinct immune protein profiles across various tauopathies.
• To identify potential protein biomarkers for differentiating tauopathies in vivo.

Main Methods:

• Analyzed 71 immune-related proteins in brain tissue from 127 individuals with diagnosed AD, CTE, PSP, CBD, and AGD.
• Used partial least square regression for unbiased clustering and identification of disease-specific proteins.
• Validated candidate biomarkers in cerebrospinal fluid (CSF) from AD and CTE cases.

Main Results:

• Identified five immune protein clusters, each correlating with a specific tauopathy (AD, CTE, PSP, CBD, AGD).
• CCL21 was identified as a key protein for CTE, FLT3L for AD, and IL13 for PSP.
• CCL21 levels were elevated in CTE CSF compared to AD CSF, supporting its potential as a biomarker.

Conclusions:

• Neuroinflammatory responses vary among tauopathies, suggesting distinct underlying mechanisms.
• Neuroinflammatory signatures hold promise for differentiating tauopathies and improving in-life diagnostic specificity.