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Approved research

Cerebral correlates of the APOE and other genetic risk factors for Alzheimer's disease in healthy middle-aged individuals

Principal Investigator: Dr Juan Gispert
Approved Research ID: 31085
Approval date: July 3rd 2019

Lay summary

The e4 allele of the APOE gene is associated to a higher risk of Alzheimer?s disease (AD). Cognitively healthy APOE-e4 carriers have been reported to display lower gray matter volume in brain regions known to be affected by AD such as the hippocampus. Yet, numerous studies have not been able to detect any significant differences or even found areas of greater grey matter volume in e4 carriers as compared to non-carriers. We aim at investigating the cerebral neuroimaging patterns associated to the APOE genotype in healthy middle-aged subjects. Converging evidence supports that Alzheimer?s disease has a long and protracted preclinical stage. The earliest cerebral alterations are thought to happen even 20 years before the onset of the symptoms. We aim at studying cerebral patterns of individuals with an increased genetic risk of developing AD in order to better characterize this preclinical stage and to reveal any potential interactions with other modifiable risk factors (hypercholesterolemia, hypertension, elevated body-mass-index, etc?) which have also been linked to the APOE-e4 genotype. We could therefore provide with novel evidence supporting primary prevention of AD. In healthy individuals, we will analyze brain regions known to be affected in AD and will seek for the cerebral fingerprint of the APOE genotype. We will also seek for associations between these brain regions and other factors also known to be affected by the APOE genotype such as high blood cholesterol among other factors known to increase the risk of both AD and cardiovascular disease. This investigation might help us understanding the underlying biological factors involved in APOE increasing the risk of these conditions. We would like to include all available individuals with a minimum of a T1-weighted magnetic resonance images and a genome-wide analysis (to obtain the APOE genotype). Additional analyses would also require other magnetic resonance image modalities and variables such as hypertension, hypercholesterolemia, body-mass-index, dietary and lifestyle questionnaires, as well as psychometric scales.