The cellular prion protein and its role in Alzheimer disease

Abstract

The cellular prion protein (PrP C ) is a membrane-bound glycoprotein especially abundant in the central nervous system (CNS). The scrapie prion protein (PrP Sc, also termed prions) is responsible of transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases which affect humans and other mammal species, although the presence of PrP C is needed for the establishment and further evolution of prions.The present work compares the expression and localization of PrP C between healthy human brains and those suffering from Alzheimer disease (AD).In both situations we have observed a rostrocaudal decrease in the amount of PrP C within the CNS, both by immunoblotting and immunohistochemistry techniques. PrP C is higher expressed in our control brains than in AD cases. There was a neuronal loss and astogliosis in our AD cases. There was a tendency of a lesser expression of PrP C in AD cases than in healthy ones. And in AD cases, the intensity of the expression of the unglycosylated band is higher than the di-and monoglycosylated bands.With regards to amyloid plaques, those present in AD cases were positively labeled for PrP C , a result which is further supported by the presence of PrP C in the amyloid plaques of a transgenic line of mice mimicking AD.The work was done according to Helsinki Declaration of 1975, and approved by the Ethics Committee

Unaltered prion protein expression in Alzheimer disease patients

“…Our results appear to be in general disagreement with the central topic of recently published studies by Velayos and co-workers 29 which indicated a tendency for lower steady state PrP C levels in the brains of AD patients compared to controls, 29 especially in the hippocampus, an outcome apparently inconsistent with previous reports of increased PrP C immunoreactivity in the temporal cortex, hippocampus (CA2) and subiculum in AD patients compared to controls. 30 Although not discussed in the context of their data, the report of Velayos and co-workers was significant in light of recent studies implicating PrP C as a major receptor that mediates the deleterious effects of oligomeric Aβ1-42 on synaptic function.…”

Cellular Prion Protein and Sexual Dimorphic Areas in Rodents. Correlates with Alzheimer Disease

“…Another finding which we have come across is that in mice the expression of the non-glycosylated band becomes more pronounced with age, above all in female mice which is in agreement with our previous findings [30]. One can probably say, by extrapolation, and based on previous findings of Velayos et al [30], that in humans, and more so in women, the greater propensity for Alzheimer's disease and the cognitive symptoms specific to the elderly may be related to the level of non-glycosylated PrPC, all this taken together with the above considerations, with regard to the frontal cortex.…”

“…One can probably say, by extrapolation, and based on previous findings of Velayos et al [30], that in humans, and more so in women, the greater propensity for Alzheimer's disease and the cognitive symptoms specific to the elderly may be related to the level of non-glycosylated PrPC, all this taken together with the above considerations, with regard to the frontal cortex. On the other hand, the incubation period of the prionopathies is shorter in female mice than in males [37].…”

“…On our part, we have observed a particular behaviour of PrPC in brains with AD. There is less expression of PrPC in patients with AD than in control cases, furthermore in AD, the non-glycosylated band is larger than the di-and monoglycosylated bands in Western blots of PrPC [30]. To this it should be added that according to statistical studies, AD is found to be more frequent in women than in men.…”

Prion protein and Alzheimer disease

“…38 (Whitehouse and Hooper NM, unpublished). A recent brief report 39 that showed a decrease of PrP C in the hippocampus, frontal cortex and temporal cortex in AD would also appear to support this. However, the number of cases (two AD and three controls) was too small for statistical analysis and whether the AD cases were sporadic and appropriately age matched with the controls not reported.…”