The APOE4 effect: Structural brain differences in Alzheimer's disease according to the age at symptom onset.

BACKGROUND
Assess how APOE genotype can differentially affect cortical and subcortical memory structures in biomarker-confirmed early and late-onset Alzheimer's Disease (EOAD-LOAD).


METHODS
Eighty-seven CSF biomarker-confirmed AD patients were classified according to their APOE genotype and age at onset. 28 were EOAD APOE4 carriers (+EOAD), 21 EOAD APOE4 non-carriers (-EOAD), 23 LOAD APOE4 carriers (+LOAD) and 15 LOAD APOE4 non-carriers (-LOAD). Grey matter (GM) volume differences were analyzed using Voxel-Based Morphometry in Papez circuit regions. Multiple regression analyses were performed to determine the relation between GM volume loss and cognition.


RESULTS
We report significantly more mammillary bodies atrophy in +EOAD compared to -EOAD. Medial temporal and posterior cingulate cortex (PCC) showed less GM in +LOAD compared to -LOAD. Medial temporal GM volume loss were also found in +EOAD when compared to -LOAD. With the exception for +EOAD, medial temporal GM was strongly associated with episodic memory in the three groups, while PCC GM volume was more related with visuospatial abilities. Visuospatial abilities and episodic memory were also associated with the anterior thalamic nucleus in -LOAD.


CONCLUSIONS
Our results show that APOE genotype has a significant effect on GM integrity as a function of age of disease onset. Specifically, while LOAD APOE4 genotype is mostly associated with increased medial temporal and parietal atrophy compared to -LOAD, for EOAD APOE4 might have a more specific effect on subcortical (mammillary body) structures. The findings suggest that APOE genotype needs to be taken into account when classifying patients by age at onset.