Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease affected brains: a possible role for apolipoprotein E in Alzheimer's disease

Amyloid deposits in Alzheimer's disease (AD) are composed of amyloid beta protein (A beta) and many other components called amyloid-associated proteins. Apolipoprotein E (apoE) is one of the most important amyloid-associated proteins. The role apoE plays in AD, however, is yet to be determined. Zn this study, we present the biochemical and histochemical nature of apoE in AD-affected brains using four monoclonal antibodies (mAbs) against apoE and newly established antibodies against the amino-terminal (anti-apoE-N), and carboxyl-terminal regions (anti-apoE-C) of apoE. Competitive ELISA and Western-blot analysis combined with thrombolytic digestion of apoE indicated that our four mAbs recognized at least two different epitopes within a 22-kDa amino-terminal domain of apoE. Using these mAbs and an anti-A beta mAb, double immunostaining showed that the majority of amyloid deposits were stained by both anti-apoE and anti-AP mAbs, but the minority of them were detected only by either anti-apoE or anti-A beta mAbs. Differences in staining properties between anti-apoE-N and anti-apoE-C were that anti-apoE-C recognized both amyloid deposits and astrocytes similar to anti-apoE mAbs, but anti-apoE-N strongly stained only astrocytes. Preliminary semi-quantitative determinations of apoE in CSF and brain homogenate showed that the amount of apoE increased in AD and Creutzfeldt-Jakob disease brains compared to normal samples. Our immunological data, using antibodies specific for the amino and carboxyl termini of apoE, suggest that apoE may, in some circumstances, initiate plaque formation, and that apoE in amyloid deposits has at least part of its amino termini cleaved out. (C) 1997 Elsevier Science B.V.