PATHOGENESIS OF ALZHEIMER-RELATED NEURITIC PLAQUES - AT8 IMMUNOREACTIVE DYSTROPHIC NEURITES PRECEDE ARGYROPHILIC NEURITES IN PLAQUES OF THEENTORHINAL REGION, HIPPOCAMPAL-FORMATION, AND AMYGDALA

The hyperphosphorylated microtubule-associated protein tau is a major component of Alzheimer-related intraneuronal cytoskeletal changes. Hyp erphosphorylated tau proteins may form straight and paired helical fil aments, which can condensate and crosslink, leading to agglomerations called neurofibrillary changes. The non-crosslinked filaments have bee n shown to precede the neurofibrillary changes in the cell body and de ndritic processes of neurons. However, Alzheimer-related cytoskeletal changes are also found in dystrophic neurites of axonal origin. In the present study, occurrence of non-crosslinked and crosslinked cytoskel etal changes in dystrophic neurites of plaques has been investigated i n the entorhinal region, hippocampal formation, and amygdala of cases at transentorhinal and limbic stages according to Braak and Braak. Con secutive 7 mu m thick paraffin sections have been stained with the Cam pbell/Switzer and Gallyas silver techniques, as well as AT8 antibody f or demonstration of beta-amyloid deposits, neurofibrillary changes, an d non-crosslinked filaments, respectively. Most beta-amyloid deposits contained neither AT8-immunoreactive nor Gallyas positive argyrophilic neurites. Furthermore, a considerable proportion of beta-amyloid depo sits displayed only AT8-immunoreactive dystrophic neurites. The findin gs indicate that AT8-immunoreactive neuronal processes located in beta -amyloid deposits precede Gallyas positive argyrophilic neurites in ne uritic plaques. Both non-crosslinked and crosslinked forms of Alzheime r-type cytoskeletal changes are likely to develop in beta-amyloid depo sits.