Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8.     

Pathology and Immunocytochemistry of a Kuru Brain

We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare "florid" plaques with surrounding vacuolation.
We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.     

Ultrastructural changes in the optic nerves of rodents with experimental Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS) or scrapie

This report describes the ultrastructural changes in the optic nerves of (1) hamsters infected with the Echigo-1 strain of Creutzfeldt-Jakob disease (CJD), (2) hamsters infected with the 263K or 22C-H strain of scrapie, and (3) mice infected with the Fujisaki strain of Gerstmann-Str?ussler-Scheinker disease (GSS). Vacuolation of myelinated fibres was present in the myelin sheaths, with splitting of myelin lamellae. These vacuoles contained typical secondary vacuoles and curled membrane fragments. Myelinated fibre vacuolation was also accompanied by an exuberant cellular reaction consisting of macrophages containing numerous mitochondria, abundant rough endoplasmic reticulum, and secondary lysosomes filled with digested myelin debris and other electron-dense material. Within macrophages, myelin fragments undergoing active digestion, lyre-like bodies and paracrystalline inclusions were frequently noted. Astrocytes and their processes were prominent; glial filaments and many mitochondria were readily detected. Proliferation of inner mesaxons was observed. Cross-sectional profiles of innumerable myelinated fibres contained membranous organelles continuous with the inner lamellae of the oligodendroglial cells. The proliferations of inner mesaxons formed whorls and loops, and intrusion of the membranous tongue of the inner mesaxon into the axoplasm was occasionally observed; dystrophic neurites were relatively numerous. In mice infected with the Fujisaki strain of GSS, fibres had undergone demyelination with stripping of the myelin lamellae, while others showed vesicular myelin degeneration.     

Brain histamine metabolism in transmissible spongiform encephalopathy (Scrapie)

Summary The histamine (Hi) content and the activity of L-histidine decarboxylase (HD) in brains of scrapie infected hamsters were measured. No significant changes in Hi levels in particular brain areas were found when compared to controls. Decreased activity of HD was found in hypothalamus (p<0.02). Increased activity of the enzyme was observed in rest of brain, which consisted mainly of thalamus and striatum (p<0.05).     

Echigo-1: a panencephalopathic strain of Creutzfeldt-Jakob disease: ultrastructural studies of the optic nerve

The Echigo-1 strain of CJD was isolated by Mori and colleagues (1989) from a case of 33-year-old female with a panencephalopathic type of CJD. An incubation period following intracerebral inoculation of hamsters with 10% cleared suspension of the Echigo-1-affected brain was approximately six months. We report here ultrastructural changes which are comparable with those in the white matter of another panencephalopathic type of CJD, the Fujisaki strain of CJD (GSS) passaged in mice. Vacuoles developed within myelinated axons: within axoplasm or within the myelin sheath and these were accompanied by exuberant reaction of macrophages and hypertrophic astrocytes. Axons underwent Wallerian degeneration and dystrophic neurites were also seen. Most important, we observed proliferation of inner mesaxons. Cross-sectional profiles of innumerable myelinated fibers contained membranous organelles which were continuous with the inner lamellae of the oligodendroglial cells. These unusual proliferations of inner mesaxon formed whorls and elaborated loops. In some axons, proliferation was so severe that loops of mesaxon filled the whole cross-section of the axon. Occasionally, we observed intrusion of the membranous tongue of the inner mesaxon into axoplasm. This study presents a second panencephalopathic model of CJD available in small laboratory rodents. It is important because this is the only such model in hamsters and it may be used for comparative studies of different strains of agent in the same host; thus far only mouse and hamster model have been available for comparative studies.     

Molecular analysis of PRNP gene in Polish population and in Creutzfeldt-Jakob disease

In our study we have examined allelic variation of codon 129 among the Polish population as well as Polish and Dutch CJD cases. The open reading frame of the PrP gene was amplified using the polymerase chain reaction (PCR). PCR product was digested with Nsp I and Mae II endonucleases and separated by 2% agarose gel electrophoresis and, finally, sequenced by the Sanger dideoxy-mediated chain-termination method. To obtain population data we have screened 109 unrelated Polish adults. There were 45% of methionine homozygotes, 16% of valine homozygotes and 3% of heterozygotes. Among Polish CJD cases, 75% were methionine homozygous, 12.5% were valine homozygous and 12.5% were heterozygous, whereas among Dutch CJD cases it was 29% of Met/Met and 71% of Met/Val genotypes.     

Proton magnetic resonance spectroscopy of primary pediatric brain tumors: neuropathological correlation

Forty-five children with primary brain tumors were evaluated by in vivo proton magnetic resonance spectroscopy (MRS) with the aim of detecting correlations between the obtained spectra and tumor malignancy and histology. All investigations were performed using a 1.5 T MR scanner (Picker) with point-resolved spectroscopic (PRESS) sequence (TR 1600 ms, TE 270 ms, NEX 256). Spectra were analyzed for N-acetylaspartate (NAA), choline containing-compounds (Cho), creatine and phosphocreatine (Cr) and lactate (Lac). The Cho/NAA ratio was the most useful parameter for differentiating between normal brain, benign and malignant tumors as well as discriminating the three main groups of pediatric brain tumors namely pilocytic astrocytoma, ependymoma and medulloblastoma. Proton MRS appears to be an important noninvasive technique in the differential diagnosis of pediatric brain tumors.     

Clinicopathological analysis of pilocytic astrocytomas and gangliogliomas in children

We present here a clinico-pathological analysis of 58 pilocytic astrocytomas (PA) and 11 gangliogliomas (GG) based on an analysis of neuronal markers (GFAP, SYN, NFP) in these two groups of neoplasms. During the retrospective review of 58 cases recognized primarily as PA, 11 verified neoplasms demonstrated strong reaction for SYN or NFP or for both antibodies. These cases were reclassified as gangliogliomas. None of 11 tumors recognized as GG were further reclassified as PA. The overall 5-year survival was 88.89% in PA and 70.00% in GG group.