Psychosis in Alzheimer’s Disease Induced by Female-Specific Gene

Psychosis in AD is associated with the female-specific APOE4 gene and is comorbid with Lewy bodies.

The Apolipoprotein E (APOE) gene can induce psychosis in subjects with a neuropathologically confirmed diagnosis of Alzheimer’s disease (AD), according to research presented at the 2017 American Academy of Neurology Annual Meeting, April 22-27, Boston, Massachusetts. However, this association was only considered significant in females.

While the APOE4 allele is one of the strongest determinants of AD, limited research exists examining the association between it and psychosis in neuropathologically confirmed AD. The development of Lewy bodies, which occurs in approximately 50% of patients with AD, was also recently found to be associated with APOE4.

In a study funded by the Canadian Institutes of Health Research, researchers from the Institute of Medical Science at the Li Ka Shing Knowledge Institute in Toronto, Ontario, Canada, studied the relationship between psychosis presentation in APOE4 and the role of Lewy body pathology using data obtained from the National Alzheimer’s Disease Coordinating Centre. They used the quick version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) to identify female and male patients with a history of psychosis during the course of their illness.

The researchers found 1509 subjects with severe AD, in whom the presence of APOE4 was associated with the development of psychotic symptoms – both delusions and hallucinations – in a gene dose-related manner. However, this effect, which reached significance for 2 alleles, was only observed in subjects with comorbid Lewy bodies and was much more pronounced in female subjects.

“The APOE4 has a female-specific gene dose effect in inducing psychosis, both delusions and hallucinations in AD,” said lead researcher Julia Kim. “The contribution of APOE4 to the development of psychosis in AD may be mediated by Lewy bodies.”


Kim J, Fischer C, Schweizer T, Munoz D. Neuropathological basis of apolipoprotein E genotype on psychosis in Alzheimer’s disease. Presented at: AAN 2017; April 22-27, 2017; Boston, Massachusetts.