Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease

Author:

Pichet Binette Alexa12ORCID,Theaud Guillaume3,Rheault François4,Roy Maggie3,Collins D Louis5ORCID,Levin Johannes67,Mori Hiroshi8,Lee Jae Hong9,Farlow Martin Rhys10,Schofield Peter1112,Chhatwal Jasmeer P13,Masters Colin L14,Benzinger Tammie1516,Morris John1516,Bateman Randall1516,Breitner John CS12,Poirier Judes12,Gonneaud Julie217,Descoteaux Maxime3,Villeneuve Sylvia125, ,

Affiliation:

1. Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada

2. Douglas Mental Health University Institute, Montreal, Canada

3. Sherbrooke Connectivity Imaging Laboratory (SCIL), Université de Sherbrooke, Sherbrooke, Canada

4. Electrical Engineering, Vanderbilt University, Nashville, United States

5. McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada

6. Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany

7. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

8. Department of Clinical Neuroscience, Osaka City University Medical School, Osaka, Japan

9. Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

10. Department of Neurology, Indiana University, Bloomington, United States

11. Neuroscience Research Australia, Sydney, Australia

12. School of Medical Sciences, UNSW Sydney, Sydney, Australia

13. Harvard Medical School, Massachusetts General Hospital, Boston, United States

14. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia

15. Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, United States

16. Department of Neurology, Washington University School of Medicine, St. Louis, United States

17. Normandie Univ, UNICAEN, INSERM, U1237, Institut Blood and Brain @ Caen-Normandie, Cyceron, Caen, France

Abstract

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

Funder

Canadian Institutes of Health Research

Jean-Louis Lévesque Foundation

Douglas Foundation

Canada Foundation for Innovation

NIA

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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