Indirect immunohistochemical studies on kidney tissue from the patient with amyloidosis showed marked staining with anti-prealbumin and anti-heredofamilial amyloid protein, but not with anti-AA or anti-kappa antisera.
Both the serum prealbumin and RBP concentrations were significantly depressed in 9 patients with amyloidosis when compared with normal controls and unaffected kin.
Amyloid deposits in several heredofamilial forms of amyloidosis are known to be chemically related to transthyretin (TTR, the plasma protein usually referred to as prealbumin).
Immunohistochemical investigation using the indirect immunoperoxidase staining with antisera to several purified amyloid fibril proteins showed a positive reaction with an antiserum to the prealbumin-related AF-amyloid in the families and one of the sporadic cases and with an antiserum to the immunoglobulin light chain amyloid (A lambda) in the other sporadic case.
Amyloid deposits in several heredofamilial forms of amyloidosis are chemically related to transthyretin (TTR, the protein usually referred to as prealbumin).
By radioimmunoassay, the serum level of prealbumin was measured in 25 patients from 12 different kinships with this dominantly inherited form of amyloidosis and 56 unaffected, but at risk, relatives from two of the kinships.
The immunoperoxidase method, the autoclave method, and a newly developed alkaline-guanidine method were used to distinguish senile (SSA) and familial types (FAP) of prealbumin-related amyloidosis in formalin-fixed, paraffin-embedded tissue sections.
Sequence analysis of the isolated peptides confirms this observation and shows that the 3 Brazilian families investigated in our study have the same prealbumin variant as individuals with amyloidosis of Swedish/American, Portuguese and Japanese origins.
Autosomal dominant amyloidosis, also known as familial amyloidotic polyneuropathy (FAP), is a late-onset disorder associated with variants of the protein prealbumin.
In recent years prealbumin has been shown to be a major component of two forms of systemic amyloid, senile systemic amyloid (SSA), and familial amyloidotic polyneuropathy (FAP).
This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbuminamyloidoses are more varied and prevalent than previously thought.
These observations indicate the same methionine for valine substitution at position 30 of the transthyretin molecule in patients with vitreous amyloidosis as seen in Swedish patients with FAP as well as in patients with FAP from Japan and Portugal, and patients of Swedish descent with FAP from the United States.
To date, seven different single amino acid mutations in the plasma protein prealbumin (transthyretin) have been found to be associated with amyloidosis and each is the result of a single nucleotide change in the prealbumin gene.
Thus, the behavior of the transmissible brain amyloidosis parallels completely that of the transthyretinamyloidoses causing familial amyloidotic polyneuropathy, in which there are 19 different point mutations, each one of which increases enormously the likelihood of configurational change of transthyretinprealbumin to amyloid.