Abstract
In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (BioFINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.
Highlights
In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline
For BioFINDER, we used resting-state functional MRI (fMRI) data from 500 subjects of the humanconnectome project (HCP) to determine a group-mean functional connectivity template that was used for combined tau vs. functional connectivity analyses similar to previous studies[24]
For our negative control (Fig. 7a, Model 1: distance-weighted tau), we found a moderate association with future tau change in Aβ+ dAD dementia (ADNI) (β = 0.252, p < 0.001, R2 = 0.064, Fig. 7b), where shorter distance was associated with higher future tau spread
Summary
In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Highly interconnected brain regions—so called hubs—showed more tau PET uptake than less well-connected regions in patients with AD, possibly because their large number of connections increases the likelihood to receive pathological tau species from remote brain regions[20]. Together, these first in vivo findings on the association between tau and brain network architecture support the hypothesis that the accumulation and propagation of pathologic tau is related to neural activity and inter-regional connectivity. Understanding the role of functional connectivity in the development and spread of tau pathology is of major clinical importance, paving the way towards targeting neural activity related mechanisms of tau pathology to halt clinical AD progression[21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
