Premium
Tau spreads through episodic memory networks in the aging brain
Author(s) -
Jagust William J.,
Adams Jen.,
Ziontz Jacob,
Cassady Kaitlin,
Maass Anne
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037502
Subject(s) - retrosplenial cortex , entorhinal cortex , temporal lobe , neuroscience , hippocampal formation , episodic memory , resting state fmri , hippocampus , cortex (anatomy) , psychology , posterior parietal cortex , voxel , semantic memory , temporal cortex , medicine , cognition , epilepsy , radiology
Background Episodic memory involves an anterior temporal (AT) network specialized for object memory and a posteromedial (PM) network specialized for spatial memory. Tau arises in transentorhinal cortex, in the AT system. These observations suggest that (1) targets of anterolateral entorhinal cortex (alEC) in the AT network should contain more tau than targets of posteromedial entorhinal cortex (pmEC) in the PM network, and (2) patterns of connectivity from the medial temporal lobe may explain tau spread into the medial parietal lobe. Method Older cognitively normal participants (mean age 76, sample sizes from 87‐123 depending on the analysis) in the Berkeley Aging Cohort Study (BACS) underwent resting state fMRI on a Siemens 3T Trio system, tau‐PET with [ 18 F]flortaucipir and Aβ PET with [ 11 C]PIB. Young adults (mean age 25, N = 55) were studied with fMRI but not PET. fMRI data was analyzed with seed‐to‐voxel and ROI‐to‐ROI approaches to define networks which were related to protein aggregates measured with PET. Results Functional connectivity patterns from alEC and pmEC reflected known AT and PM memory networks. Cortical targets of alEC demonstrated greater tau deposition than targets of pmEC; this effect was greater with higher Aβ and stronger connectivity. Retrosplenial cortex (RSC) showed stronger connectivity to the hippocampus than to alEC or pmEC, and stronger hippocampal‐RSC connectivity was associated with more tau deposition in medial parietal lobe (MPL). Higher hippocampal‐RSC connectivity and more MPL tau associated with poorer episodic memory performance. In comparison to younger individuals, older people showed de‐differentiation of these networks with evidence of alEC aberrantly connected to RSC. Segregation of AT and PM networks, measured as the scaled difference of within‐network correlations minus between‐network connections decreased as tau increased in older adults, reflecting greater functional connectivity between AT and PM networks. Conclusions These results indicate that neocortical tau preferentially arises in brain regions strongly connected to alEC as part of the AT system. Aβ potentiation may reflect early AD. MPL tau does not appear to arise directly from entorhinal cortex but from spread via the hippocampus. Functional consequences of these events included reduced network segregation and episodic memory impairment.