Partial amino acid sequence homology between an heredofamilial amyloid protein and human plasma prealbumin

Area of Science:

• Biochemistry
• Genetics
• Immunology

Background:

• Heredofamilial amyloidosis is a group of genetic disorders characterized by amyloid fibril deposition.
• The specific precursor protein for this type of amyloidosis, particularly in patients of Swedish ancestry, was not fully elucidated.

Purpose of the Study:

• To isolate and characterize the amyloid fibril protein from a patient with autosomal dominant heredofamilial amyloidosis.
• To determine if the amyloid fibril protein is related to known serum proteins, such as prealbumin.

Main Methods:

• Protein isolation and solubilization using guanidine HCl.
• Molecular weight determination, amino acid analysis, double immunodiffusion, and immunoelectrophoresis.
• Automated protein sequencing and cyanogen bromide cleavage.
• Antiserum production and immunological assays (immunohistochemistry).

Main Results:

• A low molecular weight, prealbumin-related protein was isolated from amyloid fibrils.
• Partial amino acid sequencing revealed homology with human prealbumin, starting at position 14.
• Antiserum to the amyloid protein cross-reacted with normal prealbumin and detected an abnormal prealbumin in the patient's serum.
• Immunohistochemistry confirmed prealbumin and heredofamilial amyloid protein presence in kidney tissue.

Conclusions:

• The amyloid fibril protein in this patient is an abnormal variant of prealbumin.
• This abnormal prealbumin is likely the precursor to the amyloid deposits in this form of heredofamilial amyloidosis.
• Further research is needed to understand the genetic basis and specific mutations leading to this abnormal prealbumin.