Protein aggregate formation permits millennium-old brain preservation.

Area of Science:

• Paleoproteomics
• Neuroscience
• Biochemistry

Background:

• Human proteins typically degrade rapidly after death due to autolysis and putrefaction.
• The long-term preservation of brain proteins in natural environments has been poorly understood.

Purpose of the Study:

• To investigate the long-term stability of human brain proteins.
• To explore the potential for protein aggregate preservation over extended periods.

Main Methods:

• Radiocarbon dating of a 2600-year-old human brain.
• Immunoelectron microscopy to assess neurocytoarchitecture.
• Immunoassays and mass spectrometry to identify and analyze brain proteins.
• Antibody generation to test protein immunogenicity.

Main Results:

• Discovery of 2600-year-old brain proteins, including glial fibrillary acidic protein (GFAP) and neurofilaments (Nfs).
• Preserved protein topography and immunogenicity of ancient brain proteins.
• Neurocytoarchitecture showed remarkable preservation despite tissue shrinkage.
• DNA quality was poor, preventing reliable sequencing.

Conclusions:

• Non-amyloid protein aggregates facilitate extraordinary long-term stability of brain proteins.
• Protein aggregate formation allows for the preservation of brain proteins for millennia.
• This finding has implications for understanding ancient biological materials and neurodegenerative diseases.