No association between alpha(1)-antichymotrypsin and apolipoprotein E in Alzheimer's disease and vascular dementia

Genetic studies have identified the apolipoprotein epsilon 4 allele (apoE e psilon 4) as a major risk factor for Alzheimer's disease (AD) and possibly vascular dementia (VD), however, apoE epsilon 4 is neither necessary nor su fficient to cause dementia. It has therefore been postulated that other gen etic or non-genetic factors must be involved in the manifestation of the di sease. The protein al-antichymotrypsin (ACT) is a good candidate for one su ch factor, as it is associated with amyloid deposits in Alzheimer's disease , promotes the polymerization of Ap peptide into amyloid filaments in vivo, and increases the neurotoxicity of AP peptide. In our study of a German po pulation we have analyzed the apoE and ACT genotypes in AD and VD patients and controls in an attempt to show whether the allele ACT-A is associated w ith apoE epsilon 4 not only in AD but also in VD. Our results show a clear association between apoE epsilon 4 and AD but not with VD and no associatio n between the ACT genotype and dementia, nor between the presence of both t he ACT-A allele and apoE epsilon 4 allele and AD. Assuming that the apoE ep silon 4 allele is a risk factor for AD these findings suggest that the effe ct of the ACT signal peptide polymorphism on AD, if present, is at most ver y small.