# The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer’s Disease

## TL;DR

This paper explores how the fibrinolytic system both helps and harms Alzheimer’s disease progression by affecting amyloid-beta and inflammation.

## Contribution

The first comprehensive analysis of the dual role of the fibrinolytic system in Alzheimer’s disease pathogenesis and treatment.

## Key findings

- The fibrinolytic system degrades amyloid-beta and improves the brain’s microenvironment.
- It also promotes neuroinflammation and tau hyperphosphorylation, worsening Alzheimer’s.
- The paper proposes new research directions to resolve this paradox for better treatments.

## Abstract

Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is fundamentally driven by dysregulation between amyloid-β (Aβ) production and clearance. Although multiple Aβ clearance pathways have been reported, the fibrinolytic system remains the only enzymatically validated degradation route. Notably, a striking paradox is emerging: fibrinolytic agents exhibit both neuroprotective and AD-promoting effects in clinical observations. This duality necessitates urgent investigation into the fibrinolytic system’s double-edged sword mechanism in AD pathogenesis. This review provides the first comprehensive analysis of the fibrinolytic system’s dichotomous regulatory functions in AD progression, summarizes current advancements in the pathogenesis and therapeutic interventions, and proposes novel research directions. By resolving this molecular paradox, we aim to accelerate transformative breakthroughs in AD prevention and precision medicine strategies. Fibrinolytic System: Neuroprotection vs. Pathogenesis. The fibrinolytic system alleviates AD by directly degrading Aβ and indirectly improving the microenvironment of the central nervous system and cerebrovascular system. Meanwhile, this system also accelerates AD by promoting neuroinflammation and tau hyperphosphorylation.

The online version contains supplementary material available at 10.1007/s10571-026-01699-6.