Plasma proteome profiling identifies changes associated to AD but not to FTD

Area of Science:

• Neuroscience
• Biomarker Discovery
• Proteomics

Background:

• Frontotemporal dementia (FTD) is a neurodegenerative disorder caused by frontotemporal lobar degeneration (FTLD).
• FTLD is pathologically characterized by Tau (FTLD-Tau) or TAR DNA binding protein 43 (FTLD-TDP) inclusions.
• Accurate diagnosis and monitoring of FTD require reliable plasma biomarkers.

Purpose of the Study:

• To identify plasma biomarker profiles distinguishing FTD from Alzheimer's disease (AD) and controls.
• To differentiate between FTD pathological subtypes (FTLD-Tau and FTLD-TDP).
• To correlate plasma biomarker findings with post-mortem frontal cortex protein expression in FTD.

Main Methods:

• Plasma proteins from 56 FTD patients, 57 AD patients, and 148 controls were analyzed using aptamer-based proteomics.
• Exploratory analysis of post-mortem frontal cortex tissue from FTD cases and controls was performed.
• Logistic lasso regression identified discriminatory plasma protein panels, with performance assessed via bootstrapping.

Main Results:

• Plasma protein expression profiles differed significantly between FTD, AD, and controls.
• A panel of 12 plasma proteins accurately discriminated FTD from AD (AUC: 0.99).
• No specific plasma protein profiles were identified for FTD overall or its subtypes; tissue analysis also showed no subtype differences.

Conclusions:

• A 12-plasma protein panel shows promise as a minimally invasive tool for differentiating FTD from AD.
• The identified panel appears primarily associated with AD pathophysiology.
• The heterogeneity of FTD may explain the lack of specific plasma biomarkers for FTD or its subtypes, necessitating larger, well-characterized cohort studies.