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

Franzmeier, Nicolai ; Dewenter, Anna ; Frontzkowski, Lukas ; Dichgans, Martin ; Rubinski, Anna ; Neitzel, Julia ; Smith, Ruben LU ; Strandberg, Olof LU ; Ossenkoppele, Rik LU and Buerger, Katharina , et al. (2020) In Science Advances 6(48).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
6
issue
48
article number
abd1327
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:33246962
  • scopus:85096948779
ISSN
2375-2548
DOI
10.1126/sciadv.abd1327
language
English
LU publication?
yes
id
51c9b81e-d6ce-454b-a12e-9b90c404f32c
date added to LUP
2020-12-11 09:17:08
date last changed
2024-04-17 20:45:46
@article{51c9b81e-d6ce-454b-a12e-9b90c404f32c,
  abstract     = {{<p>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.</p>}},
  author       = {{Franzmeier, Nicolai and Dewenter, Anna and Frontzkowski, Lukas and Dichgans, Martin and Rubinski, Anna and Neitzel, Julia and Smith, Ruben and Strandberg, Olof and Ossenkoppele, Rik and Buerger, Katharina and Duering, Marco and Hansson, Oskar and Ewers, Michael}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{48}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1126/sciadv.abd1327}},
  doi          = {{10.1126/sciadv.abd1327}},
  volume       = {{6}},
  year         = {{2020}},
}