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

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

doi:10.1016/j.neuron.2022.03.034

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

Neuron. 2022 Jun 15;110(12):1932-1943.e5. doi: 10.1016/j.neuron.2022.03.034. Epub 2022 Apr 19.

Authors

Wha Jin Lee¹, Jesse A Brown², Hye Ryun Kim³, Renaud La Joie², Hanna Cho⁴, Chul Hyoung Lyoo⁴, Gil D Rabinovici⁵, Joon-Kyung Seong⁶, William W Seeley⁷; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.
² Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
³ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea; Global Health Technology Research Center, College of Health Science, Korea University, Seoul 02841, South Korea.
⁴ Department of Neurology, Gangnam Severance Hospital, Seoul 06273, South Korea.
⁵ Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea; Department of Artificial Intelligence, Korea University, Seoul 02841, South Korea. Electronic address: jkseong@korea.ac.kr.
⁷ Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: bill.seeley@ucsf.edu.

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.

Keywords: Alzheimer’s disease; DTI; PET; amyloid-beta; connectome; tau.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Acceleration
Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Brain / metabolism
Cross-Sectional Studies
Humans
Positron-Emission Tomography / methods
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding