Polymorphism of the prion protein is associated with cognitive impairment in the elderly

Berr, Claudine; Richard, Florence; Dufouil, Carole; Amant, Carole; Alpérovitch, A; Amouyel, Philippe

doi:10.1212/wnl.51.3.734

Cited by 69 publications

(49 citation statements)

References 13 publications

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“…Codon 129 homozygosity is a well-known risk factor for CJD [23] and was demonstrated recently to be a risk factor in other dementia as well. Codon 129 homozygosity for methionine is associated with AD [24] and for valine with a risk of cognitive decline [25,26]. A study has demonstrated that AD brains are characterized by an increase of intraneuronal PrP c immunoreactivity compared to controls [27].…”

Section: Discussionmentioning

confidence: 99%

Total Prion Protein Levels in the Cerebrospinal Fluid are Reduced in Patients with Various Neurological Disorders

Meyne

Gloeckner

Ciesielczyk

et al. 2009

JAD

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We performed a study on levels of the total prion protein (PrP) in humans affected by different neurological diseases and assessed the influence of several factors such as age, gender, and disease severity on the cerebrospinal fluid PrP levels. PrP-ELISA technique was used to analyze cerebrospinal fluid (CSF) samples. 293 CSF samples of patients with Creutzfeldt-Jakob disease (CJD), Alzheimer's disease, dementia with Lewy-bodies, Parkinson's disease, multiple sclerosis, cerebral ischemia, generalized epileptic seizures, and meningitis and encephalitis in comparison to controls were analyzed. We found a significant reduction of CSF PrP levels in patients suffering from all neurodegenerative disorders analyzed. This group exhibited mean PrP values of 164 ng/ml while non-neurodegenerative disorder patients and healthy controls showed PrP levels of 208 ng/ml and 226 ng/ml, respectively. CSF levels correlated with disease severity in CJD, Alzheimer's disease, and dementia with Lewy-bodies. The finding of decreased PrP levels in the CSF of patients not only with CJD but also in other neurodegenerative disorders is intriguing. Age-, gender-, and genetic-specific factors might be involved in the PrP c regulation.

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Section: Discussionmentioning

confidence: 99%

Total Prion Protein Levels in the Cerebrospinal Fluid are Reduced in Patients with Various Neurological Disorders

Meyne

Gloeckner

Ciesielczyk

et al. 2009

JAD

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“…In case of polymorphism at codon 219 of the PRNP gene in which lysine is substituted for glutamic acid (E219K), the K allele was found to be protective against sporadic CJD in Asia and Pacific (Soldevila et al, 2003). Berr et al (1998) observed the correlation bet-ween the codon 129 polymorphisms and cognitive performance. Risk of cognitive impairment was increased significantly in VV individuals compared with either MV or MM subjects.…”

Section: Introductionmentioning

confidence: 98%

No association of prion protein gene polymorphisms with Alzheimer's disease in Korean population

Ahn

Kim²,

Kwon³

et al. 2006

Exp Mol Med

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The polymorphism at codon 129 (M129V) of the human prion protein gene (PRNP) is a known risk factor for Creutzfeldt-Jakob disease (CJD) in Caucasians. There are few reports of this polymorphism's effect on memory and on the risk of Alzheimer's disease (AD). The M129V genotype distributions among Asians are very different from Caucasians. Another polymorphism, codon 219 (E219K) is not found in Caucasians. We investigated two polymorphisms of PRNP, M129V (rs1799990) and E219K (rs1800014) in 297 Korean AD patients and 217 healthy subjects. The analysis of the genotype and allele distributions showed no significant difference between the AD patients and the controls in both polymorphisms (P = 0.19 genotype, P = 0.51 allele for M129V; P = 0.64 genotype, P = 0.50 allele for E219K). Also, the PRNP polym orphism s w ere not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E-ε4 (ApoE-ε4) allele. These results suggest that the PRNP genetic variants are not associated with the risk for AD in Korean population.

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“…Although reports show contradictory results, this polymorphism has been associated with different phenotypes in prion diseases and other neurodegenerative diseases [3][4][5][6][7][8] . The homozygosity for V was associated with higher risk of cognitive impairment in two large populational studies 28,29 . On the other hand, the homozygosity for M was also associated with lower scores on cognitive tests in cognitive normal population 30 .…”

Section: Discussionmentioning

confidence: 94%

“…The codon 129 polymorphism of PRNP has been associated with AD and cognitive performance in the elderly population 19,28 . Although reports show contradictory results, this polymorphism has been associated with different phenotypes in prion diseases and other neurodegenerative diseases [3][4][5][6][7][8] .…”

Section: Discussionmentioning

confidence: 99%

Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease

Smid¹,

Landemberger

Bahia³

et al. 2013

Arq. Neuro-Psiquiatr.

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Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD).ObjectiveTo describe the association between codon 129 polymorphisms and AD.MethodsWe investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE) were evaluated.ResultsCodon 129 genotype distribution in AD 45.5% methionine (MM), 42.2% methionine valine (MV), 12.1% valine (VV); and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05). There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups.ConclusionCodon 129 polymorphism is not a risk factor for AD in Brazilian patients.

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Polymorphism of the prion protein is associated with cognitive impairment in the elderly

Abstract: This observation suggests that variability of the PRNP locus may be associated with cognitive performance in the elderly. This result, if confirmed, offers potential clues for the role of PRNP in the human brain.

Cited by 69 publications

References 13 publications

Total Prion Protein Levels in the Cerebrospinal Fluid are Reduced in Patients with Various Neurological Disorders

Total Prion Protein Levels in the Cerebrospinal Fluid are Reduced in Patients with Various Neurological Disorders

No association of prion protein gene polymorphisms with Alzheimer's disease in Korean population

Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease

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