Dysfunction of the episodic memory network in the Alzheimer’s disease cascade

Lattmann R, Vockert N, Bernal J, Wesenberg J, Suksangkharn Y, Yakupov R, Schütze H, Glanz W, Incesoy E, Butryn M, Lüsebrink F, Schmid M, Stark M, Kleineidam L, Spottke A, Coenjaerts M, Brosseron F, Fliessbach K, Schneider A, Dechent P, Scheffler K, Hetzer S, Ramirez A, Laske C, Sodenkamp S, Altenstein S, Schneider LS, Gref D, Spruth EJ, Lohse A, Schott BH, Wiltfang J, Kilimann I, Goerss D, Rostamzadeh A, Priller J, Peters O, Hellmann-Regen J, Teipel S, Wagner M, Jessen F, Maass A, Ziegler G, Düzel E (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 17

Article Number: 3578

Journal Issue: 1

DOI: 10.1038/s41467-026-71831-z

Abstract

Alzheimer’s disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores from a disease progression model. Voxel-wise analyses revealed widespread loss of deactivation and activation with disease progression. Trajectories for the loss of deactivation were nonlinear, associated with amyloid- and tau-positivity and visually preceded trajectories of cognitive decline. The relationship between deactivation and cognitive decline was partly independent of neurodegeneration. Our results provide evidence that synaptic dysfunction and neurodegeneration are independent drivers of cognitive decline, providing a rationale for targeting synaptic dysfunction along the AD cascade.

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Lattmann, R., Vockert, N., Bernal, J., Wesenberg, J., Suksangkharn, Y., Yakupov, R.,... Düzel, E. (2026). Dysfunction of the episodic memory network in the Alzheimer’s disease cascade. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-71831-z

MLA:

Lattmann, René, et al. "Dysfunction of the episodic memory network in the Alzheimer’s disease cascade." Nature Communications 17.1 (2026).

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