The pathogenesis of transmissible spongiform encephalopathy: routes to the brain and the erection of therapeutic barricades

Brown, Paul

doi:10.1007/pl00000853

Cited by 22 publications

(12 citation statements)

References 47 publications

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“…It is believed that in naturally occurring prion diseases, such as scrapie in sheep and goats, CWD in deer and elk, bovine spongiform encephalopathy in cattle, and vCJD in humans, the infectious agent enters the host via the oral route. However, the mechanisms by which PrP Sc enters the CNS are not completely understood (2,7,24,42). It is believed that PrP Sc is imported into the CNS either by follicular dendritic cells (10,18) or by neurons (17,30).…”

Section: Discussionmentioning

confidence: 99%

Test for Detection of Disease-Associated Prion Aggregate in the Blood of Infected but Asymptomatic Animals

Chang

Cheng

Yin

et al. 2007

Clin Vaccine Immunol

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We have developed a sensitive in vitro assay for detecting disease-associated prion aggregates by combining an aggregation-specific enzyme-linked immunosorbent assay (AS-ELISA) with the fluorescent amplification catalyzed by T7 RNA polymerase technique (FACTT). The new assay, named aggregation-specific FACTT (AS-FACTT), is much more sensitive than AS-ELISA and could detect prion aggregates in the brain of mice as early as 7 days after an intraperitoneal inoculation of PrP Sc . However, AS-FACTT was still unable to detect prion aggregates in blood of infected mice. To further improve the detection limit of AS-FACTT, we added an additional prion amplification step (Am) and developed a third-generation assay, termed Am-A-FACTT. Am-A-FACTT has 100% sensitivity and specificity in detecting disease-associated prion aggregates in blood of infected mice at late but still asymptomatic stages of disease. At a very early stage, Am-A-FACTT had a sensitivity of 50% and a specificity of 100%. Most importantly, Am-A-FACTT also detects prion aggregates in blood of mule deer infected with the agent causing a naturally occurring prion disease, chronic wasting disease. Application of this assay to cattle, sheep, and humans could safeguard food supplies and prevent human contagion.

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Section: Discussionmentioning

confidence: 99%

Test for Detection of Disease-Associated Prion Aggregate in the Blood of Infected but Asymptomatic Animals

Chang

Cheng

Yin

et al. 2007

Clin Vaccine Immunol

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“…The relationship between the florid plaques and larger-diameter blood vessels could be a consequence of the haematogenous spread of PrPSc into the brain in vCJD (17)(18)(19). A number of observations, however, would argue against this hypothesis.…”

Section: Discussionmentioning

confidence: 86%

Florid prion protein (PrP) plaques in patients with variant Creutzfeldt‐Jakob disease (vCJD) are spatially related to blood vessels

Armstrong

Cairns

Ironside

2003

Neuroscience Res Communica

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SUMMARYThis study tested the hypothesis that variations in the density of the florid prion protein (PrP) plaques in the brain of patients with variant Creutzfeldt-Jakob disease (vCJD) were spatially related to blood vessels. In 81% of areas of the cerebral cortex sampled and in 37% of the remaining areas, which included the hippocampus, dentate gyrus, and cerebellum, there was a positive spatial correlation between the density of the florid plaques and the larger blood vessel profiles. The frequency of the positive spatial correlations was similar in different anatomical areas of the cerebral cortex and in the upper compared with the lower cortical laminae. The data support the hypothesis that the florid plaques cluster around the larger blood vessels in vCJD, the density of associated plaques increasing with vessel size. The development of florid plaques close to blood vessels may be due to factors associated with the blood vessels that enhance the aggregation of PrP to form the dense cores of florid plaques and is unlikely to reflect the haematogenous spread of PrP into the brain.

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“…Hence in vCJD, prions are believed to enter the nervous system by absorption through the gut following consumption of infected food, replication in the spleen, and neural entry via the spinal cord [14] whereas sporadic cases are less likely to have an iatrogenic aetiology, and to result from either random mutation or posttranslational modification of the PrP gene [3, 4]. The different origins of the pathogenic prions may affect the subsequent development and spread of the pathology through the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Various hypotheses have been proposed to explain how PrP sc spreads into the brain in CJD, for example, direct neural transmission from the site of infection, replication of PrP sc in the spleen followed by neural entry through the spinal cord [14], infection of gut-associated lymphoid tissue with subsequent spread to the dorsal motor nucleus of the vagus nerve [15, 16], and spread via the circulatory system [17]. In neurodegenerative disorders, such as AD, dementia with Lewy bodies (DLB), and Pick's disease (PiD), the density of the pathological changes within the cerebral cortex often varies significantly across the different cortical laminae [18–20].…”

Section: Introductionmentioning

confidence: 99%

Laminar Distribution of the Pathological Changes in Sporadic and Variant Creutzfeldt-Jakob Disease

Armstrong

2011

Pathology Research International

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The laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). First, in some cortical regions, the vacuolation (“spongiform change”) was more generally distributed across the cortex in sCJD. Second, there was greater neuronal loss in the upper cortex in vCJD and in the lower cortex in sCJD. Third, the “diffuse” and “florid” prion protein (PrPsc) deposits were more frequently distributed in the upper cortex in vCJD and the “synaptic” deposits in the lower cortex in sCJD. Fourth, there was a significant gliosis mainly affecting the lower cortex of both disorders. The data suggest that the pattern of cortical degeneration is different in sCJD and vCJD which may reflect differences in aetiology and the subsequent spread of prion pathology within the brain.

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The pathogenesis of transmissible spongiform encephalopathy: routes to the brain and the erection of therapeutic barricades

Cited by 22 publications

References 47 publications

Test for Detection of Disease-Associated Prion Aggregate in the Blood of Infected but Asymptomatic Animals

Test for Detection of Disease-Associated Prion Aggregate in the Blood of Infected but Asymptomatic Animals

Florid prion protein (PrP) plaques in patients with variant Creutzfeldt‐Jakob disease (vCJD) are spatially related to blood vessels

Laminar Distribution of the Pathological Changes in Sporadic and Variant Creutzfeldt-Jakob Disease

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