Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD.

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Keywords Apolipoprotein E, Cathepsin D, Creutzfeldt-Jakob disease, Polymorphism, Prion protein gene
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Journal Alzheimer Disease and Associated Disorders
Kovacs, G.G, Sanchez-Juan, P, Ströbel, T, Schuur, M, Poleggi, A, Nocentini, S, … Budka, H. (2010). Cathepsin D (C224T) polymorphism in sporadic and genetic creutzfeldt-jakob disease. Alzheimer Disease and Associated Disorders, 24(1), 104–107. doi:10.1097/WAD.0b013e3181ad378c