Changes in urinary proteins of unaffected individuals with a family history of frontotemporal dementia

Abstract

Frontotemporal dementia (FTD) is a common type of neurodegenerative dementia and the primary cause of dementia in individuals under 65 years old. Current studies typically consider family members carrying relevant gene mutations as genetic risk populations, while individuals with a family history of FTD but without known mutations are sometimes included as healthy controls in research, with their potential pathophysiological changes not being fully addressed. This study performed urinary proteomics analysis on individuals with a family history of FTD but without known mutations and healthy controls to investigate whether there are differential urinary proteins and biological pathways in FTD family members who remain undiagnosed with FTD or common mutations under existing diagnostic methods. The results showed 428 significantly differentially expressed proteins (P<0.01; FC[&ge;]2.0 or [&le;]0.5) between the two groups, among which multiple proteins have been reported to be involved in FTD or nervous system functions, particularly Progranulin (PGRN), recognized as an effective biomarker for FTD. The 146 enriched biological pathways (P<0.01) of differentially expressed proteins included multiple pathways directly related to neurons and the nervous system, such as glial cells. The differences in urinary proteins between individuals with a family history of FTD without known mutations and healthy controls indicate that urinary proteomics holds unique potential in exploring unknown pathogenic factors of FTD, providing a new perspective for deepening disease understanding and optimizing prevention and treatment strategies.