Selective PrP-like protein, doppel immunoreactivity in dystrophic neurites of senile plaques in Alzheimer's disease.

Doppel (Dpl) is a prion-like protein encoded by the gene PRND, which has been found downstream of the prion gene PRNP in several species. The present study examines by immunohistochemistry Dpl expression in brain samples from 10 patients with Alzheimer's disease (AD), three patients with Pick's disease, four patients with Parkinson's disease, eight patients with diffuse Lewy body disease (DLBD), six patients with sporadic Creutzfeldt-Jakob disease (CJD) methionine/methionine at the codon 129, two patients with sporadic CJD methionine/valine at the codon 129 and numerous kuru plaques in the cerebellum, one patient with fatal familial insomnia (FFI), and 10 age-matched controls. In the adult human brain, Dpl immunoreactivity was restricted to scattered granule cells of the cerebellum and scattered small granules in the cerebral cortex. Dpl immunoreactivity was seen around betaA4 amyloid deposits in neuritic plaques, but not in diffuse plaques, AD and the common form of DLBD. Neurofibrillary tangles, Pick bodies and Lewy bodies were not stained with anti-Dpl antibodies. No modifications in Dpl immunoreactivity were observed in CJD excepting those associated with accompanying senile plaques. No Dpl-positive deposits were seen in FFI. Whether Dpl in neuritic plaques may attenuate amyloid-induced oxidative stress and participate in the glial response around amyloid cores is discussed in light of the few available data on Dpl functions.

Changes in idiotypic predominance in the anti-arsonate response by priming with anti-idiotypic antibodies.

The predominant selection of CRI-A-bearing antibodies during the anti-arsonate (ARS) response of A/J mice has been used as a model to analyse the mechanism involved in the process of clonal selection and establishment of predominance. In order to assess the importance of the affinity and adaptability of CRI-A clones in this process, we tested the capability of a minor recurrent idiotype (id-1A3), present in a CRI-Aanti-ARS monoclonal antibody (65-1A3), to develop a normal anti-ARS response. Our results show that the id-1A3 predominance, established by anti-id-1A3 administration was stable during the primary and secondary anti-ARS response and that this predominance occurred concomitantly with low levels of CRI-A. Thus, a change in the idiotype predominance was achieved. In spite of the high levels of id-1A3, the anti-ARS antibody concentration, the affinity values, and the kinetics of the immune response were similar to those of the control group. All these results show that CRI-A clones are not essential in the normal development of the anti-ARS antibody response of A/J mice, and suggest that factors other than affinity could be involved in the establishment of the CRI-A predominance.