Amyloid-enhancing factor (AEF) is believed to be a crucial common pathogenetic link in diverse forms of human
amyloidosis. Passive transfer of crude
AEF is known to trigger accelerated splenic
amyloid deposition in mice. We have recently identified
AEF activity in
ubiquitin isolated from murine amyloidotic tissues. Using similar techniques we have purified
ubiquitin, from crude
Alzheimer's disease (AD) brain extracts, to apparent homogeneity. Based on the partial amino acid sequence homology, immunochemical and pathophysiological criteria, the approximately 5.5-kDa AD-derived
protein was identified as
ubiquitin (AD-
ubiquitin) with
AEF activity. Ten to twenty micrograms of this
protein per mouse, with or without CaCl2, in conjunction with four
subcutaneous injections of 0.5 ml of 1% aqueous AgNO3, induced accelerated splenic
amyloid deposition. By immunohistochemistry, using anti-mouse AA
amyloid antibody, the AD-
ubiquitin-induced
amyloid was identified as AA type. With anti-bovine
ubiquitin antibody, using similar spleen sections as above,
ubiquitin was found to co-deposit with AA
amyloid in the splenic perifollicular areas. These results strongly suggest that
ubiquitin may be involved in the pathogenesis of
amyloidosis.