Remote network for cognitive symptoms derived from tau accumulation in progressive supranuclear palsy

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Progressive supranuclear palsy (PSP) presents motor and cognitive impairments.
• The origins of cognitive deficits in PSP are unclear due to tau deposit distribution.
• Subcortical tau deposits are linked to motor symptoms, but not cognitive decline.

Purpose of the Study:

• To investigate the mechanisms of cognitive impairment in PSP.
• To explore the relationship between tau deposition, brain connectivity, and cognitive deficits.
• To identify specific cortical networks affected by tau pathology in PSP.

Main Methods:

• Utilized tau-PET (tau positron emission tomography) with a novel high-contrast probe.
• Combined tau-PET imaging with normative connectome data.
• Analyzed data from 37 PSP patients and 48 healthy controls.

Main Results:

• Tau deposition sites were functionally connected to a distinct cortical network.
• This network, independent of atrophy, overlapped with action-mode and frontoparietal networks.
• Tau deposition extent correlated with motor symptoms.
• Connectivity strength from tau sites to this network predicted cognitive deficit severity.

Conclusions:

• Cognitive deficits in PSP may arise from remote effects of tau pathology via convergent connectivity.
• This mechanism is independent of direct tissue atrophy.
• Identified a novel pathway linking tau pathology to cognitive decline in PSP.