PhD student : Mélina Regy

Title : Impact of Apolipoprotein E genotype on normal and pathological cognitive ageing

Supervisors : Julien Dumurgier, Pr. Bernard Hanseeuw

Doctoral school :ED 393 Epidémiologie et Sciences de l’Information Biomédicale, Université Paris Cité

Date of thesis defense : 11/2023

Funding: CDD

Thesis abstract : Cognitive aging can be classified as normal when one or more cognitive functions (such as memory, learning, reasoning, language, orientation) decline without consequences on an individual’s life1, or as pathological when the individual’s autonomy is affected2. This is referred to as dementia, with Alzheimer’s disease being the main cause, accounting for approximately 70% of cases3. The ε4 allele of apolipoprotein E (APOE4) is the main genetic risk factor for Alzheimer’s disease 4. However, the mechanisms explaining the association between APOE and dementia are still partially unknown, and the objective of this thesis is to explore the relationship between APOE, brain structures, and mortality in order to better understand these mechanisms.

The research conducted during the thesis has shown an impact of APOE4 on the initial volume and atrophy of gray matter brain volumes in a population of patients attending a memory center. The presence of APOE4 was associated with earlier hippocampal volume atrophy. A second study on the association between APOE and amyloid burden showed that women were more sensitive to the presence of APOE4, while in men, the presence of two APOE4 alleles was associated with a greater increase in β-amyloid peptide after the age of 75. Finally, our research also showed that the effect of APOE4 on mortality partially occurred through dementia in a cohort of subjects from the general population, whereas we did not find an effect of APOE4 on mortality in a population of patients attending a memory center.


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