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Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease

Franzmeier, Nicolai (author)
University Hospital Munich
Dewenter, Anna (author)
University Hospital Munich
Frontzkowski, Lukas (author)
University Hospital Munich
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Dichgans, Martin (author)
University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn
Rubinski, Anna (author)
University Hospital Munich
Neitzel, Julia (author)
University Hospital Munich
Smith, Ruben (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
Strandberg, Olof (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
Ossenkoppele, Rik (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Buerger, Katharina (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
Duering, Marco (author)
University Hospital Munich
Hansson, Oskar (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
Ewers, Michael (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
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 (creator_code:org_t)
American Association for the Advancement of Science (AAAS), 2020
2020
English.
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:48
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • In Alzheimer's disease (AD), the Braak staging scheme suggests a stereotypical tau spreading pattern that does, however, not capture interindividual variability in tau deposition. This complicates the prediction of tau spreading, which may become critical for defining individualized tau-PET readouts in clinical trials. Since tau is assumed to spread throughout connected regions, we used functional connectivity to improve tau spreading predictions over Braak staging methods. We included two samples with longitudinal tau-PET from controls and AD patients. Cross-sectionally, we found connectivity of tau epicenters (i.e., regions with earliest tau) to predict estimated tau spreading sequences. Longitudinally, we found tau accumulation rates to correlate with connectivity strength to patient-specific tau epicenters. A connectivity-based, patient-centered tau spreading model improved the assessment of tau accumulation rates compared to Braak stage-specific readouts and reduced sample sizes by ~40% in simulated tau-targeting interventions. Thus, connectivity-based tau spreading models may show utility in clinical trials.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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