Unaltered prion protein expression in Alzheimer disease patients

Saijo, Eri; Telling, Glenn C.

doi:10.4161/pri.5.2.16355

Cited by 17 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[64][65][66] Therefore, the reduction of PrP C seen in the aging and sporadic AD brain would likely also contribute to the increased susceptibility of of patients with no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), mild AD (mAD) and AD patients. 60 The reasons for the differences between these studies is not immediately apparent, although Saijo et al did not differentiate between sporadic and familial AD cases in their cohort making direct comparison with our data difficult. Like many of the biological changes that occur as a consequence of the pathological cascade in AD, this reduction in PrP C could simply be explained by downstream events associated with neurodegeneration.…”

Section: Regulation Of Amyloid-β Production By the Prion Proteincontrasting

confidence: 59%

Regulation of amyloid-β production by the prion protein

Griffiths

Whitehouse

Hooper

2012

Prion

View full text Add to dashboard Cite

Section: Regulation Of Amyloid-β Production By the Prion Proteincontrasting

confidence: 59%

Regulation of amyloid-β production by the prion protein

Griffiths

Whitehouse

Hooper

2012

Prion

View full text Add to dashboard Cite

“…Here we have demonstrated that PrP C is unchanged in brains from DS patients, indicating that the over-expression of APP does not alter PrP C expression in the human brain. A recent study reported that PrP C is unchanged in the AD brain [27]. However, while the cohort was well characterised in terms of diagnosis, the authors did not provide any information as to whether the AD cases were familial or sporadic.…”

Section: Discussionmentioning

confidence: 95%

Prion Protein Is Decreased in Alzheimer's Brain and Inversely Correlates with BACE1 Activity, Amyloid-β Levels and Braak Stage

et al. 2013

View full text Add to dashboard Cite

The cellular prion protein (PrPC) has been implicated in the development of Alzheimer's disease (AD). PrPC decreases amyloid-β (Aβ) production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1) activity. Contactin 5 (CNTN5) has also been implicated in the development of AD by a genome-wide association study. Here we measured PrPC and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrPC was decreased in sporadic AD compared to controls (by 49%, p = 0.014) but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217). PrPC significantly inversely correlated with BACE1 activity (rs = −0.358, p = 0.006), Aβ load (rs = −0.456, p = 0.001), soluble Aβ (rs = −0.283, p = 0.026) and insoluble Aβ (rs = −0.353, p = 0.007) and PrPC also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (rs = −0.377, p = 0.007). CNTN5 did not correlate with Aβ load (rs = 0.040, p = 0.393), soluble Aβ (rs = 0.113, p = 0.223) or insoluble Aβ (rs = 0.169, p = 0.125). PrPC was also measured in frontal cortex samples from 9 Down's syndrome (DS) and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrPC in the DS brains compared to controls (p = 0.625). These data are consistent with a role for PrPC in regulating Aβ production and indicate that brain PrPC level may be important in influencing the onset and progression of sporadic AD.

show abstract

“…Of interest to us are the controversial issues in the literature linking Aβ oligomers and PrP C (Laurén et al, 2009; Nygaard and Strittmatter, 2009; Gunther and Striitmatter, 2010; Kessels et al, 2010; Barry et al, 2011; Saijo et al, 2011; Larson et al, 2012; Um et al, 2012; Chen et al, 2013; Kudo et al, 2013; Whitehouse et al, 2013; Younan et al, 2013). A few specific examples to make the point: Kudo et al showed that Prnp (-/-) mice are resistant to the neurotoxic effect of oligomeric Aβ in vivo and in vitro (Kudo et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

Calderón‐Garcidueñas¹,

Cross²,

Franco-Lira³

et al. 2013

Front. Neurosci.

View full text Add to dashboard Cite

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrPC) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrPC and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrPC (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrPC compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.

show abstract

Unaltered prion protein expression in Alzheimer disease patients

Cited by 17 publications

References 34 publications

Regulation of amyloid-β production by the prion protein

Regulation of amyloid-β production by the prion protein

Prion Protein Is Decreased in Alzheimer's Brain and Inversely Correlates with BACE1 Activity, Amyloid-β Levels and Braak Stage

Contact Info

Product

Resources

About