Genetic Risk Marker Found for Late-Life Depression

The epsilon 4 (ε4) allele of the apolipoprotein gene (APOE) has been associated with atherosclerosis as well as cardiovascular and cerebrovascular disease but it is less clear whether there is also an association with geriatric depression.

Individuals who carry the APOE ε4, one of the most powerful predictors in neuropsychiatry, are at increased risk for developing Alzheimer's disease, early age of Alzheimer's disease onset, and more rapid progression of Alzheimer's disease symptoms.


Scientists at the University of Gothenburg (Sweden) and their international colleagues enrolled 839 women and men with an age range, 70 to 92 years and a mean age, 73.8 years. The enrollees were free from dementia and depression that underwent neuropsychiatric and neuropsychological examinations and genotyping of the APOE ε4 allele. Follow-up evaluations were conducted in 2005 and 2009.The association between APOE ε4 allele and five year incidence of depression was examined, while avoiding possible confounding effects of clinical or preclinical dementia by excluding participants who had dementia at study entry, subsequently developed dementia during the nine year follow-up period.

Blood samples were collected, and APOE (gene map locus 19q13.2) genotyping was performed by minisequencing and was successful for 100% of the consenting participants. Genotypes were obtained for the two single nucleotide polymorphisms (rs7412 and rs429358) that are used to define unambiguously ε2, ε3, and ε4 alleles. Dementia was diagnosed by geriatric psychiatrists based on symptoms rated during the neuropsychiatric examinations and information from the close informant interviews.

In 2000, major depression was diagnosed in 32 participants, and minor depression was diagnosed in 94 participants. No associations could be observed at baseline between the APOE ε4 allele and minor depression. No interactions by sex regarding the association between depression and APOE ε4 could be seen and the presence of the APOE ε4 allele was not related to 5-year or 9-year mortality. However between 2000 and 2009, 103 individuals developed dementia; 50 new cases based on the 2005 examination, 53 new cases based on the 2009 examination. In a multiple logistic regression model (including age and sex), presence of the APOE ε4 allele was associated with dementia development during 2001to 2009.

Silke Kern, MD, PhD, the lead author of the study, said, “In our study, the presence of the APOE ε4 predicted future depression, even after excluding individuals who later developed dementia. It was also related to dementia. APOE ε4 might be a marker for identifying older persons at risk to develop depression or dementia, which could be important for prevention and early detection of these common disorders.” The study was published on November 15, 2015, in the journal Biological Psychiatry.

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