Apolipoprotein(a) null phenotype is related to a delayed age at onset of Alzheimer's disease.

Apolipoprotein(a) [apo(a)] is a highly polymorphic glycoprotein which has been suggested to play a role in Alzheimer's disease (AD). Plasma lipoprotein(a) [Lp(a)] levels and the differential expression of apo(a) isoforms were analyzed in 73 sporadic AD patients compared with 73 age- and gender-matched healthy controls. The distribution of apo(a) isoforms and Lp(a) concentrations were similar in the two groups. However, we observed that AD patients with no apo(a) isoform from immunoblots (subjects with the 'null phenotype') had a mean age at onset of 76.8+/-8.8 versus 66.9+/-9.6 years of those who expressed at least one apo(a) band (P = 0.010). Multivariate analysis showed that this effect was independent of apolipoproteinE epsilon4 allele. We conclude that the expression of at least one apo(a) isoform may interact with other pathogenic mechanisms involved in controlling the age at onset of AD.