A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.
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Papassotiropoulos A, Bagli M, Kurz A, Kornhuber J, Forstl H, Maier W, Pauls J, Lautenschlager N, Heun R
A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.
Ann Neurol. 2000 Mar;47(3):399-403.
- PubMed ID
- 10716266 [ View in PubMed]
- Abstract
Cathepsin D (catD) is an intracellular acid protease possibly involved in Alzheimer's disease (AD)-related neurodegeneration through cleavage of amyloid precursor protein into amyloidogenic components. We studied whether an exonic polymorphism of the catD gene (C --> T [Ala --> Val] transition at position 224), which possibly influences pro-catD secretion and intracellular maturation of the enzyme, was associated with the risk for the development of AD in 127 demented patients and 184 controls. The catD*T allele was significantly overrepresented in demented patients (11.8%) compared with nondemented controls (4.9%). Carriers of the catD*T allele had a 3.1-fold increased risk for developing AD than noncarriers. Carriers of the apolipoprotein E (ApoE) epsilon4 allele (ApoE*4) had a 3.9-fold increased risk than non-carriers. The adjusted odds ratio for subjects with the ApoE*4 and the catD*T allele was 19.0 compared with subjects with neither of these two alleles. Our data confirm the results of a recently performed pilot study in an independent sample and suggest that the catD genotype is strongly associated with the risk for AD.