IMMUNOREACTIVITY OF PRESENILIN-1 AND TAU IN ALZHEIMERS-DISEASE BRAIN

Mutations in the presenilin-1 gene (PS-1) on chromosome 14 are causati ve for early-onset familial Alzheimer's disease (AD). In order to stud y the localization of PS-1 in human brain, a polyclonal antibody, SB63 , against a N-terminal epitope of PS-1 ((25)VRSQNDNRER-QEHND(40)), was raised in rabbits and characterized. Immunolabeling with SB63 of form alin-fixed sections of hippocampus from cases of PS-1-linked AD (PS-1 I143T (AD/A), G384A (AD/B)), sporadic AD, and controls showed a predom inant neuronal staining pattern with a stronger immunoreactivity in py ramidal neurons. Staining was mainly granular and localized in the neu ronal cell body as well as in neuronal processes. In AD some dystrophi c neurites surrounding the amyloid plaques were stained, but no immuno reactivity was observed in the amyloid core. Although PS-1 was present in tangle bearing neurons, colocalization of PS-1 and tau could not b e detected using immunofluorescence double labeling. Our data indicate that the pattern of PS-1 immunoreactivity in the hippocampus does not substantially differ between PS-1-linked AD, sporadic AD, and control s. (C) 1998 Academic Press.