No association between α1-antichymotrypsin and apolipoprotein E in Alzheimer's disease and vascular dementia

Genetic studies have identified the apolipoprotein epsilon 4 allele (apoE epsilon 4) as a major risk factor for Alzheimer's disease (AD) and possibly vascular dementia (VD), however, apoE epsilon 4 is neither necessary nor sufficient to cause dementia. It has therefore been postulated that other genetic or non-genetic factors must be involved in the manifestation of the disease. The protein al-antichymotrypsin (ACT) is a good candidate for one such 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 population 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 with 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 association between the ACT genotype and dementia, nor between the presence of both the ACT-A allele and apoE epsilon 4 allele and AD. Assuming that the apoE epsilon 4 allele is a risk factor for AD these findings suggest that the effect of the ACT signal peptide polymorphism on AD, if present, is at most very small.