ABSTRACT
The apolipoprotein A-I-associated amyloidoses are an autosomal dominant familial disorder characterized by the pathologic deposition of N-terminal fragments of mutated apo A-I molecules as fibrils within vital organs throughout the body. This chapter argues that the fibrils extracted from the kidney of a patient with renal amyloidosis contained another apo A-I mutation, the substitution of proline for leucine at position 64. It demonstrates that this alteration resulted from a one-base transition in codon 64 of the subject’s apo A-I gene. The structural basis of apo A-I amyloidogenicity and factors responsible for selective tissue deposition are presently unknown. Particular alterations in primary structure, i.e., point mutations resulting in an increased positive charge, neutral substitutions, deletions and/or insertions, may render the molecule unstable and thus prone to form fibrils. Amyloid that is deposited mainly in the kidney can be a dominant feature in certain of the familial apo A-I-related amyloidosis.
