Predicting longitudinal basal forebrain volume in the Alzheimer’s disease spectrum: the role of sex and ApoE epsilon 4 genotype

Our findings did not show the anticipated longitudinal effects of sex and ApoE ε4 on longitudinal basal forebrain volume. Only hippocampal atrophy progressed significantly faster in ApoE ε4 homozygote carriers. This dissociation may reflect stage-dependent neurodegenerative processes, with early basal forebrain vulnerability followed by more rapid hippocampal decline, as well as methodological and sample-related constraints. If replicated, these findings suggest that hippocampal measures may be more sensitive longitudinal biomarkers in ApoE ε4 homozygotes, while sex- and ApoE ε4-related effects on the cholinergic system may be more prominent at earlier disease stages.

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Publication Details

Journal
Frontiers in Neuroscience
Published
2026-02-04
DOI
https://doi.org/10.3389/fnins.2026.1730947
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Predicting longitudinal basal forebrain volume in the Alzheimer’s disease spectrum: the role of sex and ApoE epsilon 4 genotype

Alice Grazia, Fëdor Markovič Levin, Alfredo Ramirez, Michael Wagner et al.
Frontiers in Neuroscience
Dementia and Cognitive Impairment Research
article

Predicting longitudinal basal forebrain volume in the Alzheimer’s disease spectrum: the role of sex and ApoE epsilon 4 genotype

Alice Grazia, Fëdor Markovič Levin, Alfredo Ramirez, Michael Wagner, Josef Priller, Robert Perneczky, Anja Schneider, Jens Wiltfang, Oliver Peters, Emrah Düzel, Frank Jessen, Stefan J. Teipel, Christoph Laske, Annika Spottke, Katharina Buerger
article en

Abstract

Our findings did not show the anticipated longitudinal effects of sex and ApoE ε4 on longitudinal basal forebrain volume. Only hippocampal atrophy progressed significantly faster in ApoE ε4 homozygote carriers. This dissociation may reflect stage-dependent neurodegenerative processes, with early basal forebrain vulnerability followed by more rapid hippocampal decline, as well as methodological and sample-related constraints. If replicated, these findings suggest that hippocampal measures may be more sensitive longitudinal biomarkers in ApoE ε4 homozygotes, while sex- and ApoE ε4-related effects on the cholinergic system may be more prominent at earlier disease stages.

Frontiers in NeuroscienceVol. 20
University of Cologne (DE), University Hospital Bonn (DE), German Center for Neurodegenerative Diseases (DE), University Medical Center (US), Institute for Neurodegenerative Disorders (US), Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), University Hospital Cologne (DE), University of Rostock (DE), University of Göttingen (DE), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE)
University of Southern California, Northern California Institute for Research and Education, Deutsches Zentrum für Neurodegenerative Erkrankungen, Freie Universität Berlin, Universität Rostock, National Institutes of Health, University of California, San Diego
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Dementia and Cognitive Impairment Research
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