TY - JOUR
T1 - Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease
AU - Franzmeier, Nicolai
AU - Dewenter, Anna
AU - Frontzkowski, Lukas
AU - Dichgans, Martin
AU - Rubinski, Anna
AU - Neitzel, Julia
AU - Smith, Ruben
AU - Strandberg, Olof
AU - Ossenkoppele, Rik
AU - Buerger, Katharina
AU - Duering, Marco
AU - Hansson, Oskar
AU - Ewers, Michael
PY - 2020/11/27
Y1 - 2020/11/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096948779&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/sciadv.abd1327
DO - https://doi.org/10.1126/sciadv.abd1327
M3 - Article
C2 - 33246962
SN - 2375-2548
VL - 6
JO - Science advances
JF - Science advances
IS - 48
M1 - abd1327
ER -