Tau pathology in posterior DMN is related to aberrant SN‐DMN network connectivity in atypical Alzheimer's disease: Neuroimaging of atypical AD: A first joint PIA session. (7th December 2020)

• Record Type: Journal Article
• Authors: Putcha, Deepti; Eckbo, Ryan; Touroutoglou, Alexandra; Dickerson, Brad C.; Collins, Jessica A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 1
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044591
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Circumscribed patterns of pathological tau propagation along functional networks have been observed in normal aging and amnestic Alzheimer's disease (AD), including in two cognition‐relevant networks: the default mode network (DMN) and the salience network (SN). It remains unclear if atypical phenotypes of AD demonstrate a direct relationship between tau and functional connectivity within and between these networks. Method: Twenty‐six amyloid‐positive patients diagnosed with atypical phenotypes of AD (12 PCA, 10 lvPPA, and 4 dysexecutive; mean age = 66 years, 9M/17F) were examined with tau ( 18 F‐AV‐1451) PET and resting state functional MRI (rs‐fMRI). Hub regions within the DMN and SN were defined from the literature within the bilateral posterior cingulate cortex (PCC) and anterior insula (aI), respectively. ROI‐to‐ROI connectivity was calculated to determine within‐ and between‐network connectivity. Bivariate correlation analyses were conducted to determine if the magnitude of partial volume corrected tau PET signal in each network's hub region was related to the within‐network functional connectivity of the DMN and SN, as well as between the hub regions of the DMN and SN. Result: We found that higher tau signal in bilateral PCC was associated with diminished DMN connectivity (PCC to posterior angular gyrus) in both hemispheres (left: r = ‐0.50, p = 0.009; right: r = ‐0.47, p = 0.01). We did not observe any relationship between tau and functional connectivity within the SN. Our novel observation was that higher tau signal in the PCC was associated with increased connectivity between the DMN and SN within both hemispheres (left: r = 0.55, p = 0.004; right: r = 0.47, p = 0.02), with some patients demonstrating pathologically positive functional connectivity between the DMN and SN. Conclusion: Our findings support the posited relationship between tau pathology and aberrant functional network connectivity reported in aging and amnestic AD by demonstrating that higher tau burden within the PCC is related to fractured DMN connectivity and pathologically increased DMN‐SN connectivity in a group of non‐amnestic AD patients. These findings may help explain how tau deposition in key hub regions of the DMN bring about dysfunctional inter‐network connectivity with the SN, likely contributing to the cognitive and affective dysfunction observed across the clinical spectrum of AD.