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[220506 Àú³Î¹ßÇ¥] Regional A¥â-tau interactions promote onset and acceleration of Alzheimer¡¯s disease tau spreading

¾È±Ô½Ä ¦¢ 2022-05-04

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Regional A¥â-tau interactions promote onset and acceleration of Alzheimer¡¯s disease tau spreading

https://doi.org/10.1016/j.neuron.2022.03.034Get rights and content

Highlights

Network flow-based model identifies tau propagation hubs in inferior temporal gyri

Remote A¥â-tau interactions in entorhinal cortex may trigger initial tau spreading

Local A¥â-tau interactions in inferior temporal gyrus may promote tau propagation

Connectivity-based model addresses the spatial incongruity between early A¥â and tau

Summary

Amyloid-beta and tau are key molecules in the pathogenesis of Alzheimer¡¯s disease, but it remains unclear how these proteins interact to promote disease. Here, by combining cross-sectional and longitudinal molecular imaging and network connectivity analyses in living humans, we identified two amyloid-beta/tau interactions associated with the onset and propagation of tau spreading. First, we show that the lateral entorhinal cortex, an early site of tau neurofibrillary tangle formation, is subject to remote, connectivity-mediated amyloid-beta/tau interactions linked to initial tau spreading. Second, we identify the inferior temporal gyrus as the region featuring the greatest local amyloid-beta/tau interactions and a connectivity profile well suited to accelerate tau propagation. Taken together, our data address long-standing questions regarding the topographical dissimilarity between early amyloid-beta and tau deposition.




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