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Dynamic network model reveals distinct tau spreading patterns in early- and late-onset Alzheimer disease

 Wha Jin Lee  ;  Hanna Cho  ;  Min Seok Baek  ;  Han-Kyeol Kim  ;  Jae Hoon Lee  ;  Young Hoon Ryu  ;  Chul Hyoung Lyoo  ;  Joon-Kyung Seong 
 ALZHEIMERS RESEARCH & THERAPY, Vol.14(1) : 121, 2022-09 
Journal Title
Issue Date
Alzheimer Disease* / pathology ; Amyloid beta-Peptides / metabolism ; Brain / metabolism ; Cognitive Dysfunction* / metabolism ; Copper / metabolism ; Humans ; Magnetic Resonance Imaging / methods ; Positron-Emission Tomography / methods ; tau Proteins / metabolism
Alzheimer’s disease ; Amyloid ; Network community ; Positron emission tomography ; Tau
Background: The clinical features of Alzheimer's disease (AD) vary substantially depending on whether the onset of cognitive deficits is early or late. The amount and distribution patterns of tau pathology are thought to play a key role in the clinical characteristics of AD, which spreads throughout the large-scale brain network. Here, we describe the differences between tau-spreading processes in early- and late-onset symptomatic individuals on the AD spectrum.

Methods: We divided 74 cognitively unimpaired (CU) and 68 cognitively impaired (CI) patients receiving 18F-flortaucipir positron emission tomography scans into two groups by age and age at onset. Members of each group were arranged in a pseudo-longitudinal order based on baseline tau pathology severity, and potential interregional tau-spreading pathways were defined following the order using longitudinal tau uptake. We detected a multilayer community structure through consecutive tau-spreading networks to identify spatio-temporal changes in the propagation hubs.

Results: In each group, ordered tau-spreading networks revealed the stage-dependent dynamics of tau propagation, supporting distinct tau accumulation patterns. In the young CU/early-onset CI group, tau appears to spread through a combination of three independent communities with partially overlapped territories, whose specific driving regions were the basal temporal regions, left medial and lateral temporal regions, and left parietal regions. For the old CU/late-onset CI group, however, continuation of major communities occurs in line with the appearance of hub regions in the order of bilateral entorhinal cortices, parahippocampal and fusiform gyri, and lateral temporal regions.

Conclusion: Longitudinal tau propagation depicts distinct spreading pathways of the early- and late-onset AD spectrum characterized by the specific location and appearance period of several hub regions that dominantly provide tau.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Han kyeol(김한결) ORCID logo https://orcid.org/0000-0002-7650-6708
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
Ryu, Young Hoon(유영훈) ORCID logo https://orcid.org/0000-0002-9000-5563
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0002-9898-9886
Cho, Hanna(조한나) ORCID logo https://orcid.org/0000-0001-5936-1546
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