Cellular prion protein is increased in the plasma and peri‐infarcted brain tissue after acute stroke

Abstract

The physiologic properties of the normal cellular prion protein (PrPC) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrPC in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrPC as compared to healthy age‐ and gender‐matched controls (3.1 ± 1.4 vs. 1.9 ± 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrPC in the soma of peri‐infarcted neurones as well as in the endothelial cells (EC) of micro‐vessels and inflammatory cells in peri‐infarcted brain tissue from patients who survived for 2–34 days after an initial stroke. The same pattern was repeated 1–48 hr after MCAO. RT‐PCR showed increased gene expression of PrPC by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri‐nuclear and axonal PrPC staining intensity. Increased plasma PrPC seems to reflect endogenous expression in acute stroke‐affected brain tissue. Increased cellular expression in peri‐infarcted regions may influence hypoxia‐induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated. © 2006 Wiley‐Liss, Inc.

The cellular prion protein and its role in Alzheimer disease

“…Taken together, all these findings suggest that, even though the amount of PrP C is globally lower in AD cases than in control cases, the existing PrP C expressed in AD cases may suggest a protective role in Alzheimer disease. 19,[25][26][27][28][29] However, other authors 2,20 suggest that PrP C plays an important role in the pathogenesis of AD. In agreement with our results, Rezai et al 30 observed that within the frontal cortex of both AD and control cases, the expression of PrP C is higher than in the occipital cortex.…”

PrPC, the Cellular Isoform of the Human Prion Protein, Is a Novel Biomarker of HIV-Associated Neurocognitive Impairment and Mediates Neuroinflammation

“…11 A standard curve was generated from PrP C standard supplied in the kit and protein concentration was determined by an ND-1000 spectrophotometer (Thermo Scientific, Wilmington, DE). The limit of detection of the assay was 0.3 ng/ml.…”

“…It is most abundantly expressed in the CNS, where it is found constitutively on CNS cells, 8,9 the BBB, 10,11 and on infiltrating leukocytes. 11,12 PrP C localizes to the cell membrane, where it is anchored by glycosylphosphatidylinositol 13 and functions as both an adhesion molecule 14 -18 and transducer of intracellular signaling.…”

“…11,12 PrP C localizes to the cell membrane, where it is anchored by glycosylphosphatidylinositol 13 and functions as both an adhesion molecule 14 -18 and transducer of intracellular signaling. 17,19 -21 Importantly, PrP C plays a role in many of the physiological processes disrupted during HIV-1 infection.…”

Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

“…55 Previous reports have shown increased plasma PrPC concentration following stroke, and in patients with various neurodegenerative diseases. 56,57 Additionally, there is a growing body of evidence reporting neurodegenerative changes post-TBI, which may possibly allude to an association with elevated plasma PrPC levels. [58][59][60][61][62][63] In our current study, we have identified the rise in plasma levels of PrPC as a novel biomarker for detection of primary bTBI; and based on current literature search, this is the first report of such an association.…”