Epsilon4 allele carriers show altered brain activity before onset of Alzheimer’s symptoms

Healthy individuals who are at risk of Alzheimer’s disease show reduced activity in the hippocampal region of the brain when performing tasks related to forming new memories. In a study published today in the open access journal BMC Medicine, individuals carrying the apolipoprotein E (APOE) epsilon4 allele, which has previously been associated with high risk of developing Alzheimer’s disease (AD), showed altered brain activity compared to APOE epsilon3 homozygotes. According to the authors of the study, this supports the idea that certain regions of the brain exhibit functional decline associated with the AOPE epsilon4 allele, and this decline begins before the onset of AD symptoms.

Mehul Trivedi and colleagues from the University of Wisconsin Medical School and the William S. Middleton Memorial VA Hospital, Madison, United States, used functional magnetic resonance imaging (fMRI) scanning to analyse the brain activity patterns of 40 apparently healthy middle-aged individuals with a family history of AD, comparing epsilon3/4 heterozygotes with epsilon3/3 homozygotes. In this test the participants were asked to distinguish between images that they were being shown for the first time and images that they had already memorized previously in a pre-scan training session.

During the task, the epsilon3/4 heterozygotes showed reduced activation in the medial temporal lobe (MTL) of the brain, including the right hippocampus, compared to the epsilon3/3 homozygotes. There were no differences between the two groups in age, education, performance during the task or neuropsychological assessment of memory; therefore the altered brain activation seen could not have been caused by impaired cognitive function. According to the authors, “if compromised MTL function continues to be observed in healthy epsilon4 carriers, this group of subjects may represent a good study population for novel treatments designed to delay the onset or to prevent the development of AD”.