Psychotic symptoms occurring in
Alzheimer's disease (AD +
psychosis, AD + P) are a marker for a more rapidly deteriorating phenotype. We have developed a polygenic model of AD + P risk, conditioned on the presence of AD. Whether risk genes for AD itself contribute to AD + P risk is not established, although our model predicts they will not. The most important identified genetic determinant of sporadic, late-onset AD is the
apolipoprotein E epsilon 4 allele (
APOE4). The effect of
APOE4 on AD phenotype is to reduce the age of onset of AD. Prior studies examining the association of
APOE4 with AD + P have reported conflicting results. However, no prior studies have examined if
APOE4 reduces time to onset of
psychosis in AD. The objective of this study was to examine the effect of
APOE4 and alpha1-antichymotrypsin/AA (ACT/AA) genotypes on time to
psychosis onset in subjects with AD. A longitudinal study of
psychosis incidence in 316 subjects with AD with no history of current or prior psychotic symptoms at entry was undertaken.
APOE and ACT genotyping was conducted per established protocols. Data were analyzed by survival analysis and Cox proportional hazards models. There were no significant associations of
APOE or ACT genotypes with time to
psychosis onset and no significant interaction of these genotypes with time to
psychosis onset. There remained no significant associations after covarying for age, age of AD onset, degree of
cognitive impairment, gender, race, and education. This is the first study to examine the genetic prediction of
psychosis onset in AD. The findings support the hypothesis that these two genetic determinants of AD risk do not contribute to the risk of development of psychotic symptoms in AD.