Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum



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Fernández Lucas, Alberto Amable and Vaquero Zamora, Lucía and Bajo Bretón, Ricardo and Zuluaga Arias, Pilar (2022) Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum. GeroScience, 44 (1). pp. 195-209. ISSN 2509-2715, ESSN 2509-2723

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Official URL: https://doi.org/10.1007/s11357-021-00450-x


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.

Item Type:Article
Additional Information:

CRUE-CSIC (Acuerdos Transformativos 2021)

Uncontrolled Keywords:ApoE4, Cognitive deterioration, Cognitive phenotype, Healthy aging, Preclinical and prodromal Alzheimer’s disease, Amyloid markers
Subjects:Medical sciences > Medicine > Neurosciences
Medical sciences > Medicine > Psychiatry
Medical sciences > Pharmacy > Molecular biology
ID Code:70568
Deposited On:18 Feb 2022 14:04
Last Modified:21 Feb 2022 12:38

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