Fernández Lucas, Alberto AmableVaquero Zamora, LucíaBajo Bretón, RicardoZuluaga Arias, María del Pilar2023-06-222023-06-222022Fernández Lucas, A. A., Vaquero Zamora, L., Bajo Bretón, R. et al. «Apolipoprotein E Ɛ4–Related Effects on Cognition Are Limited to the Alzheimer’s Disease Spectrum». GeroScience, vol. 44, n.o 1, febrero de 2022, pp. 195-209. DOI.org (Crossref), https://doi.org/10.1007/s11357-021-00450-x.2509-271510.1007/s11357-021-00450-xhttps://hdl.handle.net/20.500.14352/71324CRUE-CSIC (Acuerdos Transformativos 2021)Whether the deleterious efects of APOE4 are restricted to the Alzheimer’s disease (AD) spectrum or cause cognitive impairment irrespectively of the development of AD is still a matter of debate, and the focus of this study. Our analyses included APOE4 genotype, neuropsychological variables, amyloid-βeta (Aβ) and Tau markers, FDG-PET values, and hippocampal volumetry data derived from the healthy controls sample of the ADNI database. We formed 4 groups of equal size (n=30) based on APOE4 carriage and amyloid-PET status. Baseline and followup (i.e., 48 months post-baseline) results indicated that Aβ-positivity was the most important factor to explain poorer cognitive performance, while APOE4 only exerted a signifcant efect in Aβ-positive subjects. Additionally, multiple regression analyses evidenced that, within the Aβ-positive sample, hippocampal volumetry explained most of the variability in cognitive performance for APOE4 carriers. These fndings represent a strong support for the so-called preclinical/prodromal hypothesis, which states that the reported diferences in cognitive performance between healthy carriers and non-carriers are mainly due to the APOE4’s capability to increase the risk of AD. Moreover, our results reinforce the notion that a synergistic interaction of Aβ and APOE4 elicits a neurodegenerative process in the hippocampus that might be the main cause of impaired cognitive performance.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal article2509-2723https://doi.org/10.1007/s11357-021-00450-xopen accessApoE4Cognitive deteriorationCognitive phenotypeHealthy agingPreclinical and prodromal Alzheimer’s diseaseAmyloid markersNeurociencias (Medicina)PsiquiatríaBiología molecular (Farmacia)2490 Neurociencias3211 Psiquiatría