HAI Book 2025 - Flipbook - Page 392
Singh-Reilly, Neha
95
Relationship between neuroinflammatory ER176-PET and functional
connectivity in Progressive Apraxia of Speech
Neha Singh-Reilly1, Irene Sintini2, Ryota Satoh2, Joseph Duffy1, Rene Utianski1, Heather Clark1,
Yehkyoung Stephens1, Val Lowe2, Keith Josephs1, Jennifer Whitwell2
1
Department of Neurology, Mayo Clinic, Rochester, MN, US
Department of Radiology, Mayo Clinic, Rochester, MN, US
2
Background: Progressive apraxia of speech (PAOS) is a neurodegenerative disease affecting programming or
planning of speech that most commonly results from a four-repeat tauopathy. Neuroinflammation plays an
important role in accelerating the disease process and has a close relationship with tau. Little is known about the
relationship between neuroinflammation and functional connectivity disruptions and the spread of
neuroinflammation across functionally connected regions.
Methods: Sixteen PAOS patients were recruited by the Neurodegenerative Research group from the Department
of Neurology, Mayo Clinic, Rochester, MN and underwent neuroinflammatory (ER176)-PET, tau (18F-flortaucipir)PET and a resting state functional MRI. Images were parcellated using the Schaefer 200 atlas for cortical regions
and the Harvard-Oxford atlas for subcortical regions. Graph theory was applied to functional connectivity
matrices to extract degree and clustering coefficients. Group-average graph theory metrics were correlated with
regional ER176-PET and flortaucipir-PET SUVRs. PET patient-specific epicenters were identified as the 2.5%
regions with the highest SUVR. To investigate connectivity-based spreading of inflammation and tau, linear
regression was applied on each patient relating the connectivity to the epicenter and the SUVR in the rest of nonepicenter regions.
Results: At the group level, both ER176-PET and flortaucipir-PET SUVRs showed a positive correlation to degree
and a negative correlation to clustering coefficient across regions. These associations were strong within cortical
regions and attenuated when subcortical regions were included (Figure 1). Patient-specific analysis showed that
stronger connectivity to flortaucipir epicenters was associated with higher regional ER176-PET signal. It was also
noted that stronger connectivity to ER176 epicenters was associated with higher regional ER176-PET signal
(Figure 2).
Discussion: Neuroinflammatory ER176-PET and flortaucipir-PET uptake were higher in regions with low clustering
coefficient, implying that both inflammation and tau are associated with disrupted local connectivity. Tau may
play an important role in facilitating the spread of neuroinflammation through connectivity.
HAI2025 - 392
