Brain and CSF Alzheimer's Biomarkers Are Associated with SERPINE1 Gene Expression

Area of Science:

• Neuroscience
• Biomarker Discovery

Background:

• SERPINE1, or plasminogen activator inhibitor (PAI), is a potential biomarker for early Alzheimer's disease (AD) detection.
• Previous studies suggest SERPINE1's role, necessitating further investigation into its levels in AD patients and those at risk.

Purpose of the Study:

• To investigate SERPINE1 levels in cerebrospinal fluid (CSF) and brain tissue.
• To correlate SERPINE1 levels with established Alzheimer's disease biomarkers and pathological stages.

Main Methods:

• Quantified CSF SERPINE1 protein levels using OLINK and immunoassay in PREVENT-AD and ADNI cohorts.
• Measured SERPINE1 mRNA levels in brain tissue using microarray and RNAseq in two independent brain banks.

Main Results:

• Pre-clinically, CSF SERPINE1 levels correlated with elevated pTau, tTau, synaptic markers, and reduced hippocampal volume.
• Cortical SERPINE1 mRNA showed a strong correlation with Braak staging in autopsy-confirmed AD, but weak correlation with amyloid plaques and tangles.

Conclusions:

• CSF SERPINE1 serves as an early biomarker for detecting AD-related pathological changes.
• Higher SERPINE1 levels are more strongly associated with tau pathology than amyloid pathology in Alzheimer's disease.