Abstract
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-β (Aβ) 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, although 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.
Highlights
Alzheimer’s disease (AD) is characterized by amyloid-b (Ab) plaques and hyperphosphorylated forms of the tau protein as neurofibrillary tangles (NFTs) (Braak and Braak, 1991)
We found a region by Ab status interaction (F(1.65) = 6.09, p=0.005), which was driven by Ab+ participants having a greater mean difference in tau deposition in regions of anterolateral EC (alEC) functional connectivity (FC) compared to outside cortical regions than did Ab- participants (t(59.53) = 2.64, p=0.01), while this difference in alEC FC compared to posteromedial entorhinal cortex (EC) (pmEC) FC regions was trending (t(56.64) = 1.90, p=0.06)
We demonstrate that patterns of EC FC predict the spatial topography and level of cortical tau deposition in a sample of cognitively normal older adult (OA), where regions with high entorhinal connectivity have more tau
Summary
Alzheimer’s disease (AD) is characterized by amyloid-b (Ab) plaques and hyperphosphorylated forms of the tau protein as neurofibrillary tangles (NFTs) (Braak and Braak, 1991). Both of these aggregated proteins can be found in the brains of cognitively normal older adults (OA), suggesting that they reflect the 10–25 year incubation period for AD (Jack et al, 2010). The mechanisms that cause tau to spread out of the EC and to other cortical regions are key to understanding, and preventing, the development of AD
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