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

## TL;DR

This study shows that SERPINE1 levels in cerebrospinal fluid and brain tissue are linked to Alzheimer’s disease biomarkers, suggesting it could be an early detection tool.

## Contribution

The study links SERPINE1 levels to tau pathology and Braak staging, offering new insights into its potential as an early Alzheimer’s biomarker.

## Key findings

- Elevated CSF SERPINE1 levels correlate with pTau, tTau, and synaptic markers in pre-clinical Alzheimer’s.
- Cortical SERPINE1 mRNA levels in AD brains correlate strongly with Braak staging but weakly with amyloid plaques.
- SERPINE1 shows stronger association with tau pathology than with amyloid formation.

## Abstract

Background: SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer’s disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers. Methods: Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue SERPINE1 mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank. Results: At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical SERPINE1 mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging. Conclusions: CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition.