Proteome-Based Plasma Biomarkers for Cognitive Dysfunction in an Androgen Deprivation Model.

Area of Science:

• Neuroscience
• Oncology
• Biochemistry

Background:

• Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer.
• ADT can lead to significant cognitive dysfunction, impacting memory, learning, and decision-making.
• There is a need for reliable biomarkers to assess ADT's cognitive effects.

Purpose of the Study:

• To identify and validate biomarkers associated with cognitive dysfunction induced by ADT.
• To investigate the impact of ADT on brain structure, function, and metabolism.
• To explore the potential of blood-based biomarkers for monitoring cognitive changes.

Main Methods:

• A mouse model was used, administering enzalutamide (an antiandrogen) to simulate ADT.
• Behavioral tests, 18F-FDG PET scans, histological analysis, and proteomic analysis (nLC-MS/MS) were performed.
• Proteins with altered expression in brain tissue were further validated in blood plasma.

Main Results:

• Enzalutamide treatment induced behavioral changes, including attention deficits and reduced social activity.
• Altered glucose metabolism and neuronal damage (decreased density, astrocyte swelling) were observed in the brains of treated mice.
• Proteomic analysis identified 29 differentially expressed proteins in the brain, with nine validated as elevated in the blood plasma of treated mice.

Conclusions:

• ADT significantly impacts cognitive function and brain health.
• Specific proteins (Pum2, Mcur1, Slc39a14, Fbxo7, Myo10, Arl6ip1, Slc8a3, Mt1, Mt3) in blood plasma show potential as biomarkers for ADT-induced cognitive dysfunction.
• Blood biomarkers could offer a non-invasive method for monitoring cognitive decline in prostate cancer patients undergoing ADT.