What can teenagers' brains tell us about Alzheimer's disease?

By studying the brains of teenagers who are carriers of an Alzheimer’s disease risk gene, researchers at King’s College London are attempting to identify the earliest processes involved in the predisposition to Alzheimer’s disease.

The Apolipoprotein E (ApoE) gene is a known risk factor for developing Alzheimer’s disease. There are three alternative forms of the same gene – ApoE ɛ4, ApoE ɛ3 and ApoE ɛ2. 

Carriers of the ɛ4 allele are at greater risk of developing late-onset Alzheimer’s disease, develop Alzheimer’s at an earlier age, and experience a more severe cognitive decline and shorter survival times. The ɛ4 allele has also been linked to the severe brain changes seen in the disease, including hippocampal atrophy (shrinkage) and alterations in the neocortex. On the other hand, the ɛ2 allele is thought to protect against the disease. 

The researchers studied 1,412 adolescents from the IMAGEN cohort who underwent MRI imaging and had blood samples tested for DNA analysis in order to determine which ApoE allele they carried. The findings were published in the Journal of Alzheimer’s Disease.

They found no differences in hippocampal volume or asymmetry between carriers and non-carriers of the ApoE ɛ4 or ɛ2 alleles. This suggests that the brain changes associated with Alzheimer’s disease in older individuals are not apparent in young people, but likely develop later on.

These findings are part of a wider project aiming to bring together data from over 4,000 people – both carriers and non-carriers of the ɛ4 allele – to understand how the genetic risk factor affects brain development throughout the life-course.

Wasim Khan, lead author and PhD student in the Department of Neuroimaging at the Institute of Psychiatry (IoP), King’s College London said: "Previous studies had suggested that the ɛ4 allele was associated with changes in infants, but in our large study, we show that these changes are not present young adolescence. We were particularly interested in this age group since adolescence is such an important phase in the maturation of human brain development."

Dr Andy Simmons, senior author of the study, also from the IoP at King’s added: "Atrophy of the hippocampus, a region of the brain crucial for memory, is a common feature of Alzheimer’s disease. Whether young people genetically at risk for Alzheimer’s manifest early changes is an important question for those interested in interventions or treatments designed to slow or stop the progression of the disease."

The research was supported by the IMAGEN project, the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King’s College London, Alzheimer Research UK and the IMI funded European Medical Information Framework.

Paper reference: Khan, W. et al ‘No Differences in Hippocampal Volume between Carriers and Non-Carriers of the ApoE  4 and 2 Alleles in Young Healthy Adolescents’ published in the Journal of Alzheimer’s Disease, 2014;40(1):37-43, doi:10.3233/JAD-131841.

For further information, please contact Seil Collins, Press Officer, Institute of Psychiatry, seil.collins@kcl.ac.uk / (+44) 0207 848 5377