Tau protein spreads through functionally connected neurons in Alzheimer’s disease: a combined MEG/PET study

Author:

Schoonhoven Deborah N123ORCID,Coomans Emma M2345ORCID,Millán Ana P15,van Nifterick Anne M123,Visser Denise2345,Ossenkoppele Rik23456,Tuncel Hayel345,van der Flier Wiesje M23,Golla Sandeep S V345,Scheltens Philip23,Hillebrand Arjan157,van Berckel Bart N M345,Stam Cornelis J13,Gouw Alida A123ORCID

Affiliation:

1. Department of Clinical Neurophysiology and MEG Center, Neurology, Amsterdam UMC location Vrije Universiteit Amsterdam , 1081 HZ Amsterdam , The Netherlands

2. Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HZ Amsterdam , The Netherlands

3. Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam , The Netherlands

4. Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HZ Amsterdam , The Netherlands

5. Amsterdam Neuroscience, Brain Imaging , 1081 HV Amsterdam , The Netherlands

6. Clinical Memory Research Unit, Lund University , 221 00 Lund , Sweden

7. Amsterdam Neuroscience, Systems and Network Neuroscience , 1081 HV Amsterdam , The Netherlands

Abstract

Abstract Recent studies on Alzheimer’s disease (AD) suggest that tau proteins spread through the brain following neuronal connections. Several mechanisms could be involved in this process: spreading between brain regions that interact strongly (functional connectivity); through the pattern of anatomical connections (structural connectivity); or simple diffusion. Using magnetoencephalography (MEG), we investigated which spreading pathways influence tau protein spreading by modelling the tau propagation process using an epidemic spreading model. We compared the modelled tau depositions with 18F-flortaucipir PET binding potentials at several stages of the AD continuum. In this cross-sectional study, we analysed source-reconstructed MEG data and dynamic 100-min 18F-flortaucipir PET from 57 subjects positive for amyloid-β pathology [preclinical AD (n = 16), mild cognitive impairment (MCI) due to AD (n = 16) and AD dementia (n = 25)]. Cognitively healthy subjects without amyloid-β pathology were included as controls (n = 25). Tau propagation was modelled as an epidemic process (susceptible-infected model) on MEG-based functional networks [in alpha (8–13 Hz) and beta (13–30 Hz) bands], a structural or diffusion network, starting from the middle and inferior temporal lobe. The group-level network of the control group was used as input for the model to predict tau deposition in three stages of the AD continuum. To assess performance, model output was compared to the group-specific tau deposition patterns as measured with 18F-flortaucipir PET. We repeated the analysis by using networks of the preceding disease stage and/or using regions with most observed tau deposition during the preceding stage as seeds. In the preclinical AD stage, the functional networks predicted most of the modelled tau-PET binding potential, with best correlations between model and tau-PET [corrected amplitude envelope correlation (AEC-c) alpha C = 0.584; AEC-c beta C = 0.569], followed by the structural network (C = 0.451) and simple diffusion (C = 0.451). Prediction accuracy declined for the MCI and AD dementia stages, although the correlation between modelled tau and tau-PET binding remained highest for the functional networks (C = 0.384; C = 0.376). Replacing the control-network with the network from the preceding disease stage and/or alternative seeds improved prediction accuracy in MCI but not in the dementia stage. These results suggest that in addition to structural connections, functional connections play an important role in tau spread, and highlight that neuronal dynamics play a key role in promoting this pathological process. Aberrant neuronal communication patterns should be taken into account when identifying targets for future therapy. Our results also suggest that this process is more important in earlier disease stages (preclinical AD/MCI); possibly, in later stages, other processes may be influential.

Funder

Stichting Alzheimer Nederland and Stichting VUmc fonds

ZonMW Memorabel, Dioraphte, Avid Radiopharmaceuticals, and Janssen Pharmaceuticals

ZonMW

ZonMW/Dutch Epilepsy Foundation

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3