P1‐137: REDUCED ENTORHINAL GRAY MATTER VOLUME IN HEALTHY AMYLOID‐NEGATIVE <i>APOE‐E4</i> HOMOZYGOTES OF THE ALFA COHORT

APOE-e4 is the major genetic risk factor for late-onset Alzheimer's Disease (LOAD) with e4 homozygotes showing earlier amyloid accumulation and onset of cognitive decline as compared to heterozygotes and e4 noncarriers [1]. The study of middle-aged healthy amyloid-free e4 homozygotes can shed light on the mechanisms through which APOE modulates the risk of AD. We aimed to determine whether APOE-e4 status has an effect on gray matter volume of healthy amyloid-negative individuals. The first 121 consecutive participants of the ALFA+ study [2] underwent 3D T1 MRI and [18F]-Flutemetamol PET brain imaging. Out of them, 87 turned out to be amyloid-negative, as assessed both by visual reading and by Centiloid quantification (<15 CL). Individuals were grouped according to the number of APOE-e4 alleles into homozygotes (N=14), heterozygotes (N=15) and non-carriers (N=58). Gray matter volume (GMV) was analyzed with Voxel Based Morphometry (VBM) using linear model that accounted for age, sex and educational level as confounders. The e4 homozygote group was compared to the heterozygote and non-carrier ones by means of one-sided t-tests (uncorrected p<0.001; k>100). Atrophy in the medial temporal lobe represents the most characteristic morphometric feature of AD. Our finding of lower GMV in middle-aged e4 homozygotes is in line with previous reports in children and adolescents [3] and add to existing literature of AD neuroimaging endopehnotypes observed, to a milder degree, in healthy APOE-e4 homozygotes [4]. Found in amyloid-negative individuals, lower entorhinal GMV can be regarded as to be a genetic trait that could contribute to their risk of developing Alzheimer's dementia. References [1] Liu et al. Nat Rev Neurol. 2013 Feb;9(2):106-18 [2] Molinuevo et al. Alzheimers Dement (N Y). 2016 Jun; 2(2): 82–92. [3] Shaw et al. Lancet Neurol. 2007 Jun;6(6):494-500. [4] Reiman et al. Proc Natl Acad Sci USA. 2005 Jun 7;102(23):8299-302.