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
- Received: June 7, 2019
- Accepted: August 31, 2019
- Accepted Manuscript published: September 2, 2019 (version 1)
© 2019, Adams et al.
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