Association between small apolipoprotein(a) isoforms and frontotemporal dementia in humans

Apolipoprotein(a) [apo(a)] is a genetically polymorphic glycoprotein that has several similarities to apolipoprotein E. However, its role as a risk factor for frontotemporal dementia (FTD) remains to be elucidated. We therefore investigated the effect of an apo(a) polymorphism on the incidence of FTD in a sample of Caucasian Italian patients. From the entire group of FTD patients (n=54), 55.6% of the subjects had at least one apo(a) low molecular weight (MW) isoform, compared to 29.9% of non-demented controls (n=77). The difference between the two groups was statistically significant (odds ratio 2.93, 95% confidence interval 1.42-6.06, P=0.003). The FTD group was further divided into sporadic (n=26) and familial (n=28) cases. Even after such dichotomization, both sporadic and familial FTD patients showed a significantly higher prevalence of low MW apo(a) isoforms than the cognitively healthy controls (P=0.011 and P=0.025, respectively). Our data suggest a role of apo(a) phenotypes of low MW in mediating susceptibility to FTD.