Jiayi Zhang (Shanghai / CN), Yuanyu Huang (Shanghai / CN), Yu Guo (Shanghai / CN), Yaru Zhang (Shanghai / CN), Huali Shen (Shanghai / CN), Jintai Yu (Shanghai / CN)
The disease spectrum of Alzheimer's Disease (AD) is characterized by a continuum that ranges from asymptomatic phases to more overt stages of cognitive decline. Early intervention during these initial stages can significantly improve patient outcomes. Staging AD based on biomarkers is crucial as it allows for the identification of disease changes before clinical symptoms manifest, thereby advancing precision medicine approaches for AD.
In our study, we utilized data independent acquisition (DIA) mass spectrometry to analyze 174 paired samples of serum and cerebrospinal fluid (CSF). Our discovery cohort included samples from three distinct preclinical AD stages (Stage I, II, III), AD-related mild cognitive impairment (MCI), and healthy controls. From these samples, we identified 2,988 CSF protein groups and 414 serum protein groups. Notably, 965 CSF proteins and 22 serum proteins demonstrated significant changes and can be considered as potential biomarkers for monitoring AD progression or for its early diagnosis.
These potential biomarkers offer insights into the molecular dynamics at play during the earliest phases of AD, suggesting potential targets for therapeutic intervention. These findings emphasize the non-linear path of pathological changes during the preclinical development of AD and provide a deeper molecular and systemic understanding that could help the management and treatment of Alzheimer's Disease. Future validation of these biomarkers in external datasets will be imperative to confirm their utility and reliability in clinical settings.