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oai:docta.ucm.es:20.500.14352/713242024-09-19T13:40:02Zcom_20.500.14352_14col_20.500.14352_15

Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum Fernández Lucas, Alberto Amable Vaquero Zamora, Lucía Bajo Bretón, Ricardo Zuluaga Arias, María del Pilar ApoE4 Cognitive deterioration Cognitive phenotype Healthy aging Preclinical and prodromal Alzheimer’s disease Amyloid markers Neurociencias (Medicina) Psiquiatría Biología molecular (Farmacia) 2490 Neurociencias 3211 Psiquiatría CRUE-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. Depto. de Medicina Legal, Psiquiatría y Patología Fac. de Medicina TRUE pub 2023-06-22T10:40:41Z 2023-06-22T10:40:41Z 2022 journal article https://hdl.handle.net/20.500.14352/71324 2509-2715 10.1007/s11357-021-00450-x 2509-2723 eng Fernández 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. Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ open access application/pdf Springer Nature