Regional Aβ-tau interactions promote onset and acceleration of Alzheimer's disease tau spreading.

Abstract

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.

• Authors: Wha Jin Lee, Jesse A Brown, Hye Ryun Kim, Renaud La Joie, Hanna Cho, Chul Hyoung Lyoo, Gil D Rabinovici, Joon-Kyung Seong, William W Seeley, Alzheimer’s Disease Neuroimaging Initiative
• Journal: Neuron (Neuron) Vol. 110 Issue 12 Pg. 1932-1943.e5 (06 15 2022) ISSN: 1097-4199 [Electronic] United States
• PMID: 35443153 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• tau Proteins

Topics

• Acceleration
• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Brain (metabolism)
• Cross-Sectional Studies
• Humans
• Positron-Emission Tomography (methods)
• tau Proteins (metabolism)