Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex (alEC) in the aging brain. The transition to Alzheimer's disease (AD) is hypothesized to involve amyloid-b (Ab) facilitated tau spread through neural connections. We contrasted functional connectivity (FC) of alEC and posteromedial EC (pmEC), subregions of EC that differ in functional specialization and cortical connectivity, with the hypothesis that alEC-connected cortex would show greater tau deposition than pmEC-connected cortex. We used resting state fMRI to measure FC, and PET to measure tau and Aβ in cognitively normal older adults. Tau preferentially deposited in alEC-connected cortex compared to pmEC-connected or non-connected cortex, and stronger connectivity was associated with increased tau deposition. FC-tau relationships were present regardless of Aβ, though strengthened with Aβ. These results provide an explanation for the anatomic specificity of neocortical tau deposition in the aging brain and reveal relationships between normal aging and the evolution of AD.
- William J Jagust
- Theresa M Harrison
- Anne Maass
- William J Jagust
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: All participants provided written informed consent. This study was approved by the Lawrence Berkeley National Laboratory institutional review board (protocol # 073H026).
- Inna Slutsky, Tel Aviv University, Israel
© 2019, Adams et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Despite extensive research on the role of the rodent medial and lateral entorhinal cortex (MEC/LEC) in spatial navigation, memory and related disease, their human homologues remain elusive. Here, we combine high-field functional magnetic resonance imaging at 7 T with novel data-driven and model-based analyses to identify corresponding subregions in humans based on the well-known global connectivity fingerprints in rodents and sensitivity to spatial and non-spatial information. We provide evidence for a functional division primarily along the anteroposterior axis. Localising the human homologue of the rodent MEC and LEC has important implications for translating studies on the hippocampo-entorhinal memory system from rodents to humans.