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- W2980645143 abstract "APOE-ε4, the greatest genetic risk factor for late-onset Alzheimer's disease (AD), has been associated to earlier beta-amyloid (Aβ) accumulation and reduced cerebral metabolism in unimpaired individuals. Low levels of cerebrospinal fluid (CSF) Aβ42 have been independently associated to cortical atrophy in cognitively healthy individuals, although some studies reported null associations. Here we hypothesized that the impact of CSF Aβ42 on cerebral gray matter volumes (GMv) is modulated by the APOE-ε4 genotype. Two-hundred-thirty-eight cognitively unimpaired individuals (mean age = 60.82, SD = 4.83), were classified in three groups according to the number of the ε4 alleles (non-carriers = 149, ε4-heterozygotes = 75, ε4-homozygotes = 14). High resolution structural MR images were acquired with a 3T scanner and analyzed with voxel-based morphometry (VBM). Episodic memory and executive functions were also assessed. We investigated the impact of continuous and categorical Aβ42 on GMv in the whole sample and subsequently analyzed the interaction with APOE-ε4. Individuals were considered Aβ positive if their CSF Aβ42 concentration was lower than 1098 pg/ml. Results were considered significant if surviving a whole-brain threshold of p<0.001 with a cluster-extent correction of 100 voxels. CSF Aβ42 concentrations did not significantly affect cognitive performance. In line with previous reports, the proportion of Aβ positive individuals was significantly higher in APOE-ε4 carriers, with a gene dose-dependent effect (χ2 = 29.39, P<0.001). In the whole sample, lower levels of CSF Aβ42 were related to lower GMv in medial prefrontal and posterior parietal areas (Fig. 1). Inclusion of continuous CSF p-tau in the model as covariate did not significantly alter these results. The association between CSF Aβ42 and GMv was significantly modulated by APOE-ε4 status in a set of brain regions, including the insula and inferior frontal areas (Fig. 2a-2b)." @default.
- W2980645143 created "2019-10-25" @default.
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- W2980645143 date "2019-07-01" @default.
- W2980645143 modified "2023-10-06" @default.
- W2980645143 title "O3-02-01: APOE- ε4 ALLELIC LOAD MODULATES THE ASSOCIATION BETWEEN CSF BETA-AMYLOID AND GRAY MATTER VOLUME IN COGNITIVELY UNIMPAIRED INDIVIDUALS" @default.
- W2980645143 doi "https://doi.org/10.1016/j.jalz.2019.06.4630" @default.
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