AMYLOID-P IMMUNOREACTIVITY PRECEDES C4D DEPOSITION ON EXTRACELLULAR NEUROFIBRILLARY TANGLES

Extracellular neurofibrillary tangles (eNFTs) are the insoluble cytosk eletal debris left behind when neurons with intracellular neurofibrill ary tangles (iNFTs) die. Reactive microglia and reactive astrocytes ga ther around eNFTs. Many inflammatory proteins are deposited in their v icinity, including activated components of the classical complement pa thway. Agents which are potential activators of the pathway include be ta-amyloid protein (A beta) and amyloid P (AP), since these in vitro a ctivators have been reported to be associated with both senile plaques (SPs) and eNFTs. To investigate the apparent order in which these pro teins are deposited, we studied by immunohistochemistry the relative a ssociation of AP, A beta, and the classical complement protein C4d wit h eNFTs in Alzheimer's disease (AD), parkinsonism-dementia complex of Guam (lytico-bodig, LB), and elderly non-demented cases. In normal eld erly cases with mild tangle development, most but not all eNFTs were A P positive. Substantially fewer eNFTs were C4d positive, and in two of the three cases no eNFTs were AP positive. In development, a high por tion of eNFTs were AP positive, and most of them were C4d positive. On ly a few were A beta positive. In severe LB cases, with dense tangle d evelopment, almost all eNFTs were AP and C4d positive, and a significa nt number were also A beta positive. AP seems to be deposited early in eNFT exposure and could therefore be a potential activator of the com plement pathway, while A beta deposition occurs relatively late in the process, and is therefore unlikely to be responsible.