Summary.
Prion protein gene polymorphism M129V represents a known risk factor for Creutzfeldt-Jakob disease. Recently, the meta-analysis revealed that homozygosity at codon 129 is connected with increased risk of Alzheimer’s disease (AD). To determine whether M129V polymorphism is a risk factor for AD we analyzed a group of early-onset, and late-onset Polish AD patients. We observed that in LOAD patients there is a statistically significant increase of MM (p = 0.0028) and decrease of MV (p = 0.0006) genotype frequency, as compared to controls. When both groups were stratified according to APOE4 status, increase of MM and decrease of MV genotype frequency were significant in the LOAD subgroup with no APOE4 (p = 0.017, and p = 0.018, respectively). In the subgroup with APOE4 allele, only MV genotype frequency was significantly lower, as com pared to controls (p = 0.035). However, no interaction was found between APOE4 status and M129V polymorphism. We conclude that MM genotype increases LOAD risk in Polish population independently from the APOE4 status.
Similar content being viewed by others
References
A Aguzzi M Polymenidou (2004) ArticleTitleMammalian prion biology: one century of evolving concepts Cell 116 313–327 Occurrence Handle14744440 Occurrence Handle1:CAS:528:DC%2BD2cXhtVals7g%3D Occurrence Handle10.1016/S0092-8674(03)01031-6
A Alperovitch I Zerr M Pocchiari E Mitrova J de Pedro Cuesta I Hegyi S Collins H Kretzschmar C van Duijn RG Will (1999) ArticleTitleCodon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease Lancet 353 1673–1674 Occurrence Handle10335789 Occurrence Handle1:STN:280:DyaK1M3ms1yhsg%3D%3D Occurrence Handle10.1016/S0140-6736(99)01342-2
C Berr F Richard C Dufouil C Amant A Alperovitch P Amouyel (1998) ArticleTitlePolymorphism of the prion protein is associated with cognitive impairment in the elderly: the EVA study Neurology 51 734–737 Occurrence Handle9748018 Occurrence Handle1:CAS:528:DyaK1cXmtlOlu7g%3D
VM Casadei C Ferri E Calabrese LM Grimaldi M Franceschi F Veglia F Licastro C Mariani (2001) ArticleTitlePrion protein gene polymorphism and Alzheimer’s disease: one modulatory trait of cognitive decline? J Neurol Neurosurg Psychiatry 71 279–280 Occurrence Handle11488277 Occurrence Handle1:STN:280:DC%2BD3MvktF2nsw%3D%3D Occurrence Handle10.1136/jnnp.71.2.279
J Collinge (1999) ArticleTitleVariant Creutzfeldt-Jakob disease Lancet 354 317–323 Occurrence Handle10440324 Occurrence Handle1:STN:280:DyaK1Mzms12gtA%3D%3D Occurrence Handle10.1016/S0140-6736(99)05128-4
O Combarros M Sanchez-Guerra J Llorca A Alvarez-Arcaya J Berciano N Pena C Fernandez-Viadero (2000) ArticleTitlePolymorphism at codon 129 of the prion protein gene is not associated with sporadic AD Neurology 55 593–595 Occurrence Handle10953203 Occurrence Handle1:CAS:528:DC%2BD3cXmsFSqt74%3D
R Del Bo GP Comi R Giorda M Crimi F Locatelli F Martinelli-Boneschi U Pozzoli E Castelli N Bresolin G Scarlato (2003) ArticleTitleThe 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects J Neurol 250 688–692 Occurrence Handle12796830 Occurrence Handle1:CAS:528:DC%2BD3sXnvVKju7k%3D Occurrence Handle10.1007/s00415-003-1057-5
Del Bo R, Scarlato M, Ghezzi S, Martinelli-Boneschi F, Fenoglio C, Galimberti G, Galbiati G, Virgilio R, Galimberti D, Ferrarese C, Scarpini E, Bresolin N, Comi GP (2005) Is M129V of PRNP gene associated with Alzheimer’s disease? A case-control study and a meta-analysis. Neurobiol Aging. 2005 Aug 11 [Epub ahead of print]
B Dermaut EA Croes R Rademakers M Van den Broeck M Cruts A Hofman CM van Duijn C Van Broeckhoven (2003) ArticleTitlePRNP Val129 homozygosity increases risk for early-onset Alzheimer’s disease Ann Neurol 53 409–412 Occurrence Handle12601712 Occurrence Handle1:CAS:528:DC%2BD3sXit1ynur0%3D Occurrence Handle10.1002/ana.10507
I Ferrer R Blanco M Carmona B Puig R Ribera MJ Rey T Ribalta (2001) ArticleTitlePrion protein expression in senile plaques in Alzheimer’s disease Acta Neuropathol (Berl) 101 49–56 Occurrence Handle1:CAS:528:DC%2BD3MXhtValurs%3D
E Golanska K Hulas-Bigoszewska E Rutkiewicz M Styczynska B Peplonska M Barcikowska J Bratosiewicz-Wasik PP Liberski (2004) ArticleTitlePolymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD Neurology 62 313–315 Occurrence Handle14745079 Occurrence Handle1:CAS:528:DC%2BD2cXhtFSjuw%3D%3D
G Gossrau B Herting S Mockel A Kempe R Koch H Reichmann JB Lampe (2006) ArticleTitleAnalysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson’s disease J Neural Transm 113 331–337 Occurrence Handle15997418 Occurrence Handle1:CAS:528:DC%2BD28XhtVajt7k%3D Occurrence Handle10.1007/s00702-005-0329-x
BH Kim HG Lee JK Choi JI Kim EK Choi RI Carp YS Kim (2004) ArticleTitleThe cellular prion protein (PrPC) prevents apoptotic neuronal cell death and mitochondrial dysfunction induced by serum deprivation Brain Res Mol Brain Res 124 40–50 Occurrence Handle15093684 Occurrence Handle1:CAS:528:DC%2BD2cXjt1Cgsrk%3D Occurrence Handle10.1016/j.molbrainres.2004.02.005
G Kurzawski K Safranow J Suchy D Chlubek JR Scott J Lubinski (2002) ArticleTitleMutation analysis of MLH1 and MSH2 genes performed by denaturing high-performance liquid chromatography J Biochem Biophys Methods 51 89–100 Occurrence Handle11879922 Occurrence Handle1:CAS:528:DC%2BD38XhslWju74%3D Occurrence Handle10.1016/S0165-022X(02)00003-9
JE McCormack HN Baybutt D Everington RG Will JW Ironside CJ Manson (2002) ArticleTitlePRNP contains both intronic and upstream regulatory regions that may influence susceptibility to Creutzfeldt-Jakob Disease Gene 288 139–146 Occurrence Handle12034503 Occurrence Handle1:CAS:528:DC%2BD38XjvFGiur0%3D Occurrence Handle10.1016/S0378-1119(02)00466-3
S Mead MP Stumpf J Whitfield JA Beck M Poulter T Campbell JB Uphill D Goldstein M Alpers EM Fisher J Collinge (2003) ArticleTitleBalancing selection at the prion protein gene consistent with prehistoric kurulike epidemics Science 300 640–643 Occurrence Handle12690204 Occurrence Handle1:CAS:528:DC%2BD3sXjtVymu7s%3D Occurrence Handle10.1126/science.1083320
MS Palmer AJ Dryden JT Hughes J Collinge (1991) ArticleTitleHomozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease Nature 352 340–342 Occurrence Handle1677164 Occurrence Handle1:CAS:528:DyaK3MXltFWrt7w%3D Occurrence Handle10.1038/352340a0
C Petchanikow GP Saborio L Anderes MJ Frossard MJ Olmedo C Soto (2001) ArticleTitleBiochemical and structural studies of the prion protein polymorphism FEBS Lett 509 451–456 Occurrence Handle11749972 Occurrence Handle1:CAS:528:DC%2BD3MXptFymu74%3D Occurrence Handle10.1016/S0014-5793(01)03147-7
R Petraroli G Vaccari M Pocchiari (2000) ArticleTitleA rapid and efficient method for the detection of point mutations of the human prion protein gene (PRNP) by direct sequencing J Neurosci Methods 99 59–63 Occurrence Handle10936643 Occurrence Handle1:CAS:528:DC%2BD3cXlsFCisLo%3D Occurrence Handle10.1016/S0165-0270(00)00216-8
M Riemenschneider N Klopp W Xiang S Wagenpfeil C Vollmert U Muller H Forstl T Illig H Kretzschmar A Kurz (2004) ArticleTitlePrion protein codon 129 polymorphism and risk of Alzheimer disease Neurology 63 364–366 Occurrence Handle15277640 Occurrence Handle1:CAS:528:DC%2BD2cXlsV2jt7Y%3D
A Sakudo DC Lee S Li T Nakamura Y Matsumoto K Saeki S Itohara K Ikuta T Onodera (2005) ArticleTitlePrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line Biochem Biophys Res Commun 328 14–19 Occurrence Handle15670743 Occurrence Handle1:CAS:528:DC%2BD2MXmvFarug%3D%3D Occurrence Handle10.1016/j.bbrc.2004.12.132
PD Sasieni (1997) ArticleTitleFrom genotypes to genes: doubling the sample size Biometrics 53 1253–1261 Occurrence Handle9423247 Occurrence Handle1:STN:280:DyaK1c%2FosFagsw%3D%3D Occurrence Handle10.2307/2533494
K Schwarze-Eicker K Keyvani N Gortz D Westaway N Sachser W Paulus (2005) ArticleTitlePrion protein (PrPc) promotes beta-amyloid plaque formation Neurobiol Aging 26 1177–1182 Occurrence Handle15917101 Occurrence Handle1:CAS:528:DC%2BD2MXks1CntLw%3D Occurrence Handle10.1016/j.neurobiolaging.2004.10.004
M Styczynska D Religa A Pfeffer E Luczywek B Wasiak G Styczynski B Peplonska T Gabryelewicz M Golebiowski M Kobrys M Barcikowska (2003) ArticleTitleSimultaneous analysis of five genetic risk factors in Polish patients with Alzheimer’s disease Neurosci Lett 344 99–102 Occurrence Handle12782337 Occurrence Handle1:CAS:528:DC%2BD3sXktFWltrw%3D Occurrence Handle10.1016/S0304-3940(03)00438-5
A Tahiri-Alaoui AC Gill P Disterer W James (2004) ArticleTitleMethionine 129 variant of human prion protein oligomerizes more rapidly than the valine 129 variant: implications for disease susceptibility to Creutzfeldt-Jakob disease J Biol Chem 279 31390–31397 Occurrence Handle15131108 Occurrence Handle1:CAS:528:DC%2BD2cXlslOrs7Y%3D Occurrence Handle10.1074/jbc.M401754200
CM van Duijn N Delasnerie-Laupretre C Masullo I Zerr R de Silva DP Wientjens JP Brandel T Weber V Bonavita M Zeidler A Alperovitch S Poser E Granieri A Hofman RG Will (1998) ArticleTitleCase-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993–95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD) Lancet 351 1081–1085 Occurrence Handle9660576 Occurrence Handle1:STN:280:DyaK1czit1SisQ%3D%3D Occurrence Handle10.1016/S0140-6736(97)09468-3
JD Wadsworth EA Asante M Desbruslais JM Linehan S Joiner I Gowland J Welch L Stone SE Lloyd AF Hill S Brandner J Collinge (2004) ArticleTitleHuman prion protein with valine 129 prevents expression of variant CJD phenotype Science 306 1793–1796 Occurrence Handle15539564 Occurrence Handle1:CAS:528:DC%2BD2cXhtVKitb%2FN Occurrence Handle10.1126/science.1103932
C Zekanowski D Religa K Safranow A Maruszak V Dziedziejko M Styczynska M Gacia M Golan B Peplonska D Chlubek J Kuznicki M Barcikowska (2005) ArticleTitleThe –22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer’s disease in Poland J Neural Transm 112 839–845 Occurrence Handle15480851 Occurrence Handle1:CAS:528:DC%2BD2MXjvVSqt7w%3D Occurrence Handle10.1007/s00702-004-0218-8
C Zekanowski M Styczynska B Peplonska T Gabryelewicz D Religa J Ilkowski B Kijanowska-Haladyna S Kotapka-Minc S Mikkelsen A Pfeffer A Barczak E Luczywek B Wasiak M Chodakowska-Zebrowska K Gustaw J Laczkowski T Sobow J Kuznicki M Barcikowska (2003) ArticleTitleMutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer’s disease in Poland Exp Neurol 184 991–996 Occurrence Handle14769392 Occurrence Handle1:CAS:528:DC%2BD2cXhtVSitr8%3D Occurrence Handle10.1016/S0014-4886(03)00384-4
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gacia, M., Safranow, K., Styczyńska, M. et al. Prion protein gene M129 allele is a risk factor for Alzheimer’s disease. J Neural Transm 113, 1747–1751 (2006). https://doi.org/10.1007/s00702-006-0540-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-006-0540-4