Are Alzheimer neurofibrillary tangles insoluble polymers?

Area of Science:

• Neuroscience
• Biochemistry

Background:

• Alzheimer's disease is characterized by the accumulation of paired helical filaments (PHF) in neurofibrillary tangles.
• Current bulk isolation methods for PHF include sodium dodecyl sulfate (SDS) treatment (Method I) and heating with SDS and beta-mercaptoethanol (Method II).

Purpose of the Study:

• To compare the characteristics of PHF isolated using two different methods.
• To investigate the solubility and polypeptide composition of PHF based on isolation techniques.

Main Methods:

• Isolation of PHF from Alzheimer's disease brain tissue using two distinct methods (Method I and Method II).
• Analysis of isolated PHF via SDS-polyacrylamide gel electrophoresis and immunoblotting with anti-PHF monoclonal antibodies.
• Assessment of PHF degradation using proteinase-K digestion.

Main Results:

• PHF isolated by Method I showed polypeptides ranging from 45 to 62 kilodaltons, while PHF from Method II were excluded from the gel.
• Both PHF preparations were digestible with proteinase-K, but Method I PHF degraded more rapidly.
• These results indicate that PHF solubility is dependent on the isolation procedure.

Conclusions:

• The solubility of paired helical filaments (PHF) in Alzheimer's disease is influenced by the isolation methodology.
• PHF may not be entirely insoluble polymers of covalently crosslinked polypeptides as previously assumed.