Human microglial cells synthesize albumin in brain

Area of Science:

• Neuroscience
• Biochemistry

Background:

• Albumin is a multifunctional plasma protein primarily synthesized in the liver.
• Albumin binds and transports amyloid beta (Abeta), a key factor in Alzheimer's disease (AD), and inhibits Abeta polymerization.
• While non-hepatic albumin transcription is known, protein-level synthesis outside the liver is rarely confirmed.

Purpose of the Study:

• To investigate the de novo synthesis of albumin in human microglial cells.
• To determine if microglial activation affects albumin synthesis and secretion.

Main Methods:

• Pilot study of the Human Brain Proteome Project.
• Analysis of microglial cells in human brain tissue.
• Treatment of microglial cells with amyloid beta (Abeta(1-42)) and lipopolysaccharide (LPS) to induce activation.

Main Results:

• First report of de novo albumin synthesis in human microglial cells.
• Microglial activation by Abeta(1-42) or LPS significantly enhanced albumin synthesis and secretion.
• Albumin secreted by microglia inhibits Abeta polymerization and may increase Abeta clearance.

Conclusions:

• Human microglial cells synthesize albumin in the brain.
• Microglial activation boosts albumin production, potentially mitigating AD pathology.
• Microglia play a protective role in AD through albumin secretion, impacting Abeta polymerization and clearance.