Synergistic effects of the Aβ/fibrinogen complex on synaptotoxicity, neuroinflammation, and blood-brain barrier damage in Alzheimer's disease models.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ), hyperphosphorylated tau, chronic neuroinflammation, blood-brain barrier (BBB) damage, and synaptic dysfunction, leading to neuronal loss and cognitive deficits. Vascular proteins, including fibrinogen, extravasate into the brain, further contributing to damage and inflammation. Fibrinogen's interaction with Aβ is well-established, but how this interaction contributes to synaptic dysfunction in AD is unknown.

Methods

Organotypic hippocampal cultures (OHC) were exposed to Aβ42 oligomers, fibrinogen, or Aβ42/fibrinogen complexes. Synaptotoxicity was analyzed by Western blot. Aβ42 oligomers, fibrinogen, or their complexes were intracerebroventricularly injected into mice. Histopathological AD markers, s

SUBMITTER: Simoes-Pires EN 

PROVIDER: S-EPMC12061846 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature