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Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease

Journal Article


Abstract


  • The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma- secretases). Cathepsin D is an intracellular protease with in-vitro beta- secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P1 = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E �� 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E �� 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Publication Date


  • 1999

Citation


  • Papassotiropoulos, A., Bagli, M., Feder, O., Jessen, F., Maier, W., Rao, M. L., . . . Heun, R. (1999). Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease. Neuroscience Letters, 262(3), 171-174. doi:10.1016/S0304-3940(99)00071-3

Scopus Eid


  • 2-s2.0-0033548409

Web Of Science Accession Number


Start Page


  • 171

End Page


  • 174

Volume


  • 262

Issue


  • 3

Place Of Publication


Abstract


  • The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma- secretases). Cathepsin D is an intracellular protease with in-vitro beta- secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P1 = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E �� 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E �� 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Publication Date


  • 1999

Citation


  • Papassotiropoulos, A., Bagli, M., Feder, O., Jessen, F., Maier, W., Rao, M. L., . . . Heun, R. (1999). Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease. Neuroscience Letters, 262(3), 171-174. doi:10.1016/S0304-3940(99)00071-3

Scopus Eid


  • 2-s2.0-0033548409

Web Of Science Accession Number


Start Page


  • 171

End Page


  • 174

Volume


  • 262

Issue


  • 3

Place Of Publication