Neurology -- Correspondence for Golanska et al., 62 (2) 313-315

Correspondence published:

Polymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD: Katell Peoc'h, Nicole Lauprêtre, Stéphanie Chasseigneaux and Jean-Louis Laplanche (28 June 2004)

Polymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD 28 June 2004

Katell Peoc'h,
AP-HP et Paris 5
Service de Biochimie, Hôpital Lariboisière, 2 Rue A Paré, 75475 Paris Cedex 10,
Nicole Lauprêtre, Stéphanie Chasseigneaux and Jean-Louis Laplanche
Send Correspondence to journal:
Re: Polymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD

katell.peoch{at}lrb.ap-hop-paris.fr Katell Peoc'h, et al.

Golanska et al [1] assessed the association of PRND polymorphisms with the occurrence and age at onset of Alzheimer Disease (AD). They determined the PRND sequence in 79 probable AD patients. They found that the Met/Met 174 genotype of PRND was significantly over-represented in 33 early onset AD patients (i.e. before 70 years of age). The PRND gene is polymorphic at codon 174 in humans [2,3]. This gene encodes the Doppel protein, which is physiologically expressed in the testis. [4]
We determined that PRND was not related to the genetic susceptibility to human prion diseases, as confirmed by others. [2,3] We also established the PRND genotype 174 frequency in 29 patients with sporadic neuropathologically proven early onset AD (range: 18-69 y, average: 48.9 y) using restriction fragment length polymorphisms analysis. [2] The PRND 174 Met/Met genotype was present in only 0.17 of our AD patients aged less than 70 (versus 0.42 in Golanska et al.), whereas 0.24 were Thr/Thr and 0.59 Thr/Met. The frequency of the codon 174 alleles was respectively Thr: 0.53 and Met: 0.47 (n= 58 chromosomes). These results were not significantly different to those obtained in a non-demented French population [2] for genotypes (174 Met/Met: 0.19, 174 Thr/Thr: 0.20 and 174 Thr/Met: 0.61 ; p= .90, c2 test) and alleles (Thr: 0.51 and Met: 0.49; n=212 chromosomes; p=.74, c2 test). In another study, there was no association found between PRND and AD in 103 probable patients before 70 years of age. [5]
The discrepancy may be related to the geographical origin of the patients--Polish and French--to the choice of either probable or certain AD, or to the small size of the populations studied. To elucidate a possible role of PRND in the AD physiopathology, the frequency of the genotype of the 174 codon in early onset AD patients has to be established in larger populations of certain AD patients. References 1) Golanska E, Hulas–Bigoszewska K, Rutkiewicz E, et al. Polymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD. Neurology 2004; 62: 313-315 2) Peoc'h K, Guerin C, Brandel JP, et al. First report of polymorphisms in the prion-like protein gene (PRND): implications for human prion diseases. Neurosci Lett. 2000 2;286(2):144-148. 3) Peoc'h K, Serres C, Frobert Y, et al. The human "prion-like" protein Doppel is expressed in both Sertoli cells and spermatozoa. J Biol Chem. 2002 8;277(45):43071-43078. 4) Mead S, Mahal SP, Beck J, et al. Sporadic-but not variant-Creutzfeldt- Jakob disease is associated with polymorphisms upstream of PRNP exon 1. Am J Hum Genet. 2001;69(6):1225-1235. 5) Infante J, Llorca J, Rodero L, et al. Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease.Neurosci Lett. 2002 8;332(3):213-215.