1/4. Golgi and electronmicroscopic studies of spongiform encephalopathy.Golgi impregnations of cerebral biopsies from two patients suffering from Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) revealed striking loss of dendritic spines of pyramidal neurons and unusual focal spherical distensions of dendritic and axonal processes. light and electronmicroscopic studies disclosed spongiform changes, which seemed to be caused by intracytoplasmic vacuoles and expansion of the plasmalemmal membranes of neurons and astrocytes. Although the diagnostic biopsies were performed at a markedly symptomatic stage of the disease, there was no evidence of neuronal cell loss. Neuronal changes in Golgi impregnations of cerebral cortex from hamsters infected with scrapie were essentially identical to those in the human biopsies. The loss of dendritic spines of pyramidal cells and spherical swellings of axons and dendrites thus seem to be characteristic of spongiform encephalopathies, and probably account in part for the clinical neurologic manifestations, which may be severe in the relative absence of neuronal death.- - - - - - - - - - ranking = 1keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
2/4. Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease).Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD.- - - - - - - - - - ranking = 0.024173289916684keywords = spongiform (Clic here for more details about this article) |
3/4. Induction of beta (A4)-amyloid in primates by injection of Alzheimer's disease brain homogenate. Comparison with transmission of spongiform encephalopathy.Amyloid plaques, associated with argyrophilic dystrophic neurites, and cerebral amyloid angiopathy (CAA), but no neurofibrillary tangles, were found in the brains of three middle-aged marmoset monkeys that had been injected intracerebrally (ic) 6-7 yr earlier with brain tissue from a patient with early-onset Alzheimer's disease. Such changes were not found in the brains of three age-matched control marmosets. Immunochemically the amyloid plaques and CAA stained with antibody to beta (A4)-protein. The plaques and CAA displayed dichroic birefringence when stained with congo red and viewed under polarized light. beta (A4)-amyloid plaques and CAA were also found in the brain of one of two marmosets injected ic 6 yr previously with brain tissue from a patient with prion disease with concomitant beta (A4)-amyloid plaques and CAA. An occasional beta (A4)-amyloid plaque was found in the brains of two of four marmosets injected ic > 4.5 yr previously with brain tissue from three elderly patients, two of whom had suspected (but untransmitted) CJD. No beta (A4)-amyloid plaques or CAA were found in six marmosets who were older than the injected animals, in four marmosets that had not developed spongiform encephalopathy (SE) having been injected several years previously with human brain tissue from three younger patients with suspected or atypical prion disease, or in 10 younger marmosets who had undergone various neurosurgical procedures. Seventeen marmosets injected in the same way with brain tissue from patients or animals with SE developed SE 17-49 mo after injection. These results suggest that beta (A4)-amyloidosis is a transmissible process comparable to the transmissibility of SE.- - - - - - - - - - ranking = 0.97582671008332keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
4/4. Myelinated axon undergoes complete demyelination in the panencephalopathic--but it is merely subjected to the wallerian degeneration in the polioencephalopathic type of transmissible spongiform encephalopathies.We report here on axon and myelin changes in panencephalopathic type of Creutzfeldt-Jakob disease as opposed to polioencephalopathic models of scrapie. In CJD, myelinated axons presented various pathological changes. Initially the myelin sheath was separated by cytoplasmic tongues into several concentric bands. Cellular processes penetrated between layers of myelin and lifted away the outermost lamellae. Then a complicated labyrinth of concentric cellular processes, clearly belonging to either astrocytes or macrophages invested myelinated axons. In terminal stages axons completely denuded of myelin were seen in the centre of a concentric network of cellular processes or spirals of myelin were seen surrounded by such processes. The myelin fragments penetrated into astrocytes or macrophages where they underwent final digestion. macrophages containing fragments of axons, paracrystalline lamellar bodies and myelin debris were abundant in this model. In two models of scrapie myelin dilatation, not unlike that seen in the panencephalopathic type of CJD was observed. Several altered axons were also seen, but these presented only typical features of wallerian degeneration. Even the most damaged fibres consisted of "empty" vacuoles (the axon itself was lost) surrounded by a narrow rim of oligodendroglial cytoplasm. Thus, myelinated fibre degeneration in this polioencephalopathic model merely represents the sequel to preceding neuronal degeneration. In conclusion, it seems that myelinated fibres are eventually denuded of myelin in the panencephalopathic type of CJD but undergo wallerian degeneration in polioencephalopathic types of scrapie. Because myelin dilatation is observed in both pan- and polioencephalopathic type of TSE and because their formation is probably mediated by cytokines released from astrocytes and microglia, we hypothesised that this mechanism operates early in the fibre destruction and must be supplemented later in the course of the disease by other, currently unknown mechanisms.- - - - - - - - - - ranking = 0.048346579833368keywords = spongiform (Clic here for more details about this article) |