Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.

This is the protocol for a review and there is no abstract. The objectives are as follows: 1. To review the effectiveness of supported employment compared to other approached to vocational rehabilitation and treatment as usual. 2. Secondary objectives are to establish how far: a. fidelity to the IPS model affects the effectiveness of supported employment, b. the effectiveness of supported employment can be augmented by the addition of other interventions.

Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls.Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels.One limitation of the study was the different smoking prevalence between patient groups and controls, which may have confounded the findings for MDD patients. In all, the present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson's disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP.

The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) were studied based on 30 cases of multiple system atrophy (MSA), including striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and Shy-Drager syndrome. GCIs were widely spread throughout the central nervous system, including the striatonigral and olivopontocerebellar systems. Inclusion-bearing cells appeared to be oligodendrocytes which usually had larger and lighter nuclei than those of normal-looking oligodendrocytes. The distribution of GCIs was similar in all cases, irrespective of the degrees of OPCA and SND, but the frequency of GCIs varied from case to case. We classified all the cases into two categories based on the degree of neuropathological changes of SND (mild and severe) and, independently, into three groups based on that of OPCA (minimal, moderate and severe), i.e., a total of six groups. An association between the frequency of GCIs and the severity of the lesions was obtained. For example, many GCIs were seen the cerebellar white matter in the cases in which OPCA was not histologically confirmed. More GCIs were seen in the cases with moderate OPCA. In the cases with severe OPCA, GCIs were rarer and smaller, in proportion to the devastation of fibers; no GCIs were seen in the cases with more severe OPCA. The incidence of GCIs showed a positive correlation to the severity of OPCA but not that of SND in the corticopontine tracts, of both OPCA and SND in the pyramidal tracts, and of SND but not of OPCA in the pencil fibers of the putamen. It is suggested that GCIs may represent either a change synchronous with neuronal degeneration or a phenomenon preceding neuronal changes, especially in the cerebellar white matter. Thus, they may represent the early changes in MSA and may be a useful neuropathological hallmark for diagnosis of MSA, even in cases with minimal OPCA and SND.