Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging
- 1German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany
Abstract
Episodic memory decline is a common feature of cognitively normal aging, but its extent varies markedly across individuals. Although entorhinal tau pathology is thought to be a key contributor to episodic memory impairment, the neural mechanisms linking early tau accumulation to memory differences remain unclear. Grid-cell computations in the entorhinal cortex, which provide scaffolds for organizing experiences into episodic memories, offer one candidate mechanism. Here, we combined virtual-reality functional MRI, multivariate analysis, tau PET, and delayed word-list recall in cognitively normal older adults to test whether tau-related alterations in entorhinal coding are associated with worse episodic memory. Weaker left entorhinal grid-cell-like signal was associated with poorer memory performance, and individuals with higher left entorhinal tau burden showed weaker grid-cell-like signal. This association was specific to the canonical six-fold signal and was not explained by entorhinal volume, mean diffusivity, or intracortical myelination. A cross-sectional Bayesian mediation analysis further demonstrated that bilateral medial temporal tau burden is related to memory indirectly through left entorhinal grid-cell-like signal. Together, these findings provide evidence that entorhinal grid codes may constitute a functional pathway linking tau accumulation to memory variability in normal aging.
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BibTeX
@misc{segen2026entorhinal,
title = {{Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging}},
author = {V. Segen and T. Belge Bernard and G. Callau Navarro and P. Bahrd and N. Behrenbruch and B. Schumann-Werner and S. Schwarck and B. Garcia-Garcia and H. Barthel and O. Sabri and M. C. Kreissl and E. Duzel and A. Maass and T. Wolbers},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747192},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747192v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging
AU - V. Segen
AU - T. Belge Bernard
AU - G. Callau Navarro
AU - P. Bahrd
AU - N. Behrenbruch
AU - B. Schumann-Werner
AU - S. Schwarck
AU - B. Garcia-Garcia
AU - H. Barthel
AU - O. Sabri
AU - M. C. Kreissl
AU - E. Duzel
AU - A. Maass
AU - T. Wolbers
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747192
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747192v1
AB - Episodic memory decline is a common feature of cognitively normal aging, but its extent varies markedly across individuals. Although entorhinal tau pathology is thought to be a key contributor to episodic memory impairment, the neural mechanisms linking early tau accumulation to memory differences remain unclear. Grid-cell computations in the entorhinal cortex, which provide scaffolds for organizing experiences into episodic memories, offer one candidate mechanism. Here, we combined virtual-reality functional MRI, multivariate analysis, tau PET, and delayed word-list recall in cognitively normal older adults to test whether tau-related alterations in entorhinal coding are associated with worse episodic memory. Weaker left entorhinal grid-cell-like signal was associated with poorer memory performance, and individuals with higher left entorhinal tau burden showed weaker grid-cell-like signal. This association was specific to the canonical six-fold signal and was not explained by entorhinal volume, mean diffusivity, or intracortical myelination. A cross-sectional Bayesian mediation analysis further demonstrated that bilateral medial temporal tau burden is related to memory indirectly through left entorhinal grid-cell-like signal. Together, these findings provide evidence that entorhinal grid codes may constitute a functional pathway linking tau accumulation to memory variability in normal aging.
ER -