Parkinson's disease is characterized by a progressive degeneration of dopaminergic neurons in the midbrain, yet the cause of this neuronal loss is still unknown. It has been hypothesized that Parkinson's disease could be the consequence of accelerated ageing. In order to reveal a possible common process during ageing and Parkinson's disease neurodegeneration, catecholaminergic neurons of five anatomical regions of the brainstem (substantia nigra, central grey substance, ventral tegmental area, peri- and retrorubral area, and locus coeruleus) have been quantified using immunohistochemical staining for tyrosine hydroxylase (TH) on regularly spaced sections, between the rostral and caudal poles of the mesencephalon and in the rostral pole of the pons, in post-mortem samples of 21 control subjects who died at ages 44-110 years. No statistically significant loss of TH positive neurons was observed in the older subjects, either in the substantia nigra or in the other midbrain regions that are known to degenerate to a lesser degree in Parkinson's disease. Furthermore, in the later regions no neuronal loss was observed from age 44 to 80 years, indicating that this result is not dependent on the inclusion of 'supernormal' very old people. These results suggest that from age 44 to 110 years, ageing in control adults is not, or is scarcely, accompanied by catecholaminergic cell loss in the midbrain and hence Parkinson's disease is probably not caused by an acceleration of a degenerative process during ageing.

The objective was to characterize a rapidly progressive subtype of Alzheimer's disease (rpAD). Multicenter (France, Germany, Japan, Spain) retrospective analyses of neuropathologically confirmed rpAD cases initially classified as prion disease due to their clinical phenotype were performed. Genetic properties, cerebrospinal fluid biomarkers, neuropathology, and clinical features were examined. Eighty-nine patients were included (median survival 10 months). APOE and PRNP codon 129 genotype distribution paralleled a healthy control group. APOE ε4 homozygosity was absent. Cerebrospinal fluid biomarkers were abnormal, but within a range as expected for classic AD, except for proteins 14-3-3, which were detectable in 42%. Thus, evidence of the existence of rpAD is accumulating. The APOE profile is intriguing, suggesting that this very rapid disease form might represent a distinct subtype of Alzheimer's disease.

A retroviral element (multiple sclerosis-associated retrovirus, MSRV) defining a family of genetically inherited endogenous retroviruses (human endogenous retrovirus type W, HERV-W) has been characterized in cell cultures from patients with multiple sclerosis. Recently, MSRV retroviral particles or the envelope recombinant protein were shown to display superantigen activity in vitro, but no animal model has yet been set up for studying the pathogenicity of this retrovirus. In the present study, the pathogenicity of different sources of MSRV retroviral particles has been evaluated in a hybrid animal model: severe combined immunodeficiency (SCID) mice grafted with human lymphocytes and injected intraperitoneally with MSRV virion or mock controls. MSRV-injected mice presented with acute neurological symptoms and died within 5 to 10 days post injection. Necropsy revealed disseminated and major brain hemorrhages, whereas control animals did not show abnormalities (P <.001). In ill animals, reverse transcriptase-polymerase chain reaction (RT-PCR) analyses showed circulating MSRV RNA in serum, whereas overexpression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma was evidenced in spleen RNA. Neuropathological examination confirmed that hemorrhages occurred prior to death in multifocal areas of brain parenchyma and meninges. Further series addressed the question of immune-mediated pathogenicity, by inoculating virion to SCID mice grafted with total and T lymphocyte-depleted cells in parallel: dramatic and statistically significant reduction in the number of affected mice was observed in T-depleted series (P <.001). This in vivo study suggests that MSRV retroviral particles from MS cultures have potent immunopathogenic properties mediated by T cells compatible with the previously reported superantigen activity in vitro, which appear to be mediated by an overexpression of proinflammatory cytokines.

No abstract