Serum Clearance Rate of Senile Amyloid Related Apolipoprotein A-II is Accelerated with Increasing Age in Senescence Accelerated Mouse (SAM)

Abstract

A unique senile amyloid fibril protein has been isolated from an inbred strain of mice, SAM-P/l (senescence accelerated mouse-prone) (1), established in our laboratory as a model of accelerated senescence (2,3). This amyloid protein, termed “ASSAM”, has a molecular weight of 8,700 and deposits extracellularly, with advancing age, in all tissues, except the brain and bone marrow (1, 4, 5). Using specific antiserum against ASSAM, we found that apo A-II apolipoprotein in mouse high density lipoprotein (HDL) is a serum precursor of murine senile amyloidosis (6,7). Apo A-II deposits as ASSAM without degradation (6) and also decreases in concentration with advancing age (8). We determined the primary structure of ASSAM (9) and also those of apo A-II purified from amyloid resistant slc;ICR mice (10) and SAM-R/1 (senescence accelerated mouse-resistant) (11), and SAM-P/l (11), respectively. Interestingly we found one amino acid substitution at position 5, which was proline in SAM-R/1 and ICR apo A-II, while it was glutamine in SAM-P/l HDL.