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1: Ann Neurol. 2000 Mar;47(3):399-403.Links
Comment in:
Ann Neurol. 2001 Apr;49(4):544-5.

A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.

Papassotiropoulos A, Bagli M, Kurz A, Kornhuber J, Förstl H, Maier W, Pauls J, Lautenschlager N, Heun R.

Department of Psychiatry, University of Bonn, Germany.

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.

PMID: 10716266 [PubMed - indexed for MEDLINE]