BETA-AMYLOID PROTEIN-CONTAINING INCLUSIONS IN SKELETAL-MUSCLE OF APOLIPOPROTEIN-E-DEFICIENT MICE

The tibialis anterior muscle and soleus muscle of apolipoprotein-E-def icient mice were examined by light and electron microscopy. By light m icroscopy, sarcoplasmic inclusions were seen in tibialis anterior musc le and 40% of type 2 myofibers were affected in all animals oz,er 8 mo nths of age, These inclusions reacted for nonspecific esterase, cytoch rome oxidase, and myoadenylate deaminase and were also Periodic acid S chiff positive and stained basophilic with hematoxylin. Moreover, they reacted immunocytochemically with an antibody specific to fragment 17 to 24 of the published sequence of Alzheimer's cerebrovascular amyloi d peptide. Immunoreactivity tons lost when the antibody was adsorbed w ith the appropriate synthetic peptide. Ultrastructurally, the inclusio ns consisted of tubular arrays and were similar to those observed in h uman muscle in several pathological conditions. In type 1 myofibers of both tibialis anterior and soleus muscle, however, mitochondrial abno rmalities including an increase in their number and size were detected bat tubular aggregates were not seen, These large mitochondria posses sed an electron-dense inner chamber with an increased number of tightl y packed cristae. Tbe results obtained suggest that in these mice ther e is a disturbed lipid metabolism in skeletal muscle fibers that manif ests itself with an accumulation of phospholipid in the form of sarcop lasmic reticulum tubules lit the type 2 fibers and enlarged mitochondr ia with tightly packed cristae In the type I fibers, In addition, beta -amyloid protein was closely associated with the accumulated tubules a nd vesicles of sarcoplasmic reticulum and may represent dysregulation of amyloid precursor protein metabolism.