NF-KAPPA-B IMMUNOREACTIVITY IS OBSERVED IN ASSOCIATION WITH BETA-A4 DIFFUSE PLAQUES IN PATIENTS WITH ALZHEIMERS-DISEASE

Transcription factor NF-kB is widely expressed in the nervous system a nd, particularly, in synaptic terminals. Increased NF-kB expression in synaptosomes has been observed as a result of activity, and beta A4 d eposition. In the present study we have examined NF-kB immunoreactivit y, by means of NF-kB p65 immunohistochemistry, in the brains of seven patients with Alzheimer's disease, two patients with Creutzfeldt-Jakob disease associated with PrP amyloid deposition, and seven age-matched controls. Our purpose was to examine possible NF-kB induction associa ted to beta A4 or PrP deposition in these diseases. Punctate NF-kB imm unoreactivity was constantly found in the neuropil of diffuse beta A4 deposits but not in dystrophic neurites of senile plaques. In addition , NF-kB immunoreactivity was found in the nuclei of neurons, but not i n the nuclei of reactive astrocytes, in the vicinity of diffuse plaque s, thus suggesting NF-kB translocation to the nucleus. Finally, a few neurons with neurofibrillary degeneration showed increased cytoplasmic NF-kB immunoreactivity probably secondary to abnormal compartmentatio n or impaired transport of NF-kB. No similar modifications in NF-kB im munoreactivity were observed in association with PrP deposits in patie nts with Creutzfeldt-Jakob disease. Since it has been suggested that t he presence of NF-kB in synapses map indicate the existence of a new p athway of gene transcription, the present results support the concept that this pathway may be activated by the deposition of beta A4 in dif fuse plaques in Alzheimer's disease.