Medial Parietal Tau Deposition is Associated with Hippocampal-Retrosplenial Functional Connectivity
Post by Shireen Parimoo
What's the science?
One of the hallmarks of Alzheimer’s disease pathology is the accumulation of misfolded tau protein, which begins in the transentorhinal region of the medial temporal lobe (MTL). Tau is thought to spread trans-synaptically between regions that are anatomically connected with the anterolateral entorhinal cortex (alERC), before spreading to the rest of the neocortex. Recent work suggests that tau might propagate from the MTL to functionally connected regions like the medial parietal cortex, which is part of the posteromedial memory network through its connectivity with the posteromedial entorhinal cortex (pmERC). It is important to better understand whether the functional connectivity between MTL regions and medial parietal cortex is associated with the spread of tau and episodic memory decline. This week in The Journal of Neuroscience, Ziontz and colleagues investigated the relationship between medial parietal tau accumulation and functional connectivity of MTL regions with the medial parietal lobe.
How did they do it?
Ninety-seven cognitively normal older adults (60–93 years old) were recruited from the Berkeley Aging Cohort Study and completed tests of verbal and visuospatial episodic memory. Participants also underwent a resting-state functional magnetic resonance imaging scan and a positron emission tomography scan, which allowed the authors to examine functional connectivity and amyloid/tau deposition in the brain, respectively. Functional connectivity was assessed between the hippocampus, alERC, and pmERC in the MTL and the retrosplenial cortex in the medial parietal lobe. The authors examined tau pathology in the entorhinal and inferior temporal cortices of the MTL, and in the medial parietal lobe, which included the retrosplenial cortex, posterior cingulate cortex, and precuneus regions. Specifically, they quantified tau deposition based on the signal magnitude of flortaucipir, a tracer that binds to tau protein in the brain. Lastly, they used the PiB tracer to examine amyloid-beta deposition in the medial parietal lobe and in the whole brain.
What did they find?
The retrosplenial cortex was functionally connected with the hippocampus and pmERC, but not with the alERC. Functional connectivity between these regions was not related to episodic memory. On the other hand, higher connectivity of the retrosplenial cortex with the hippocampus – but not with the alERC or pmERC – was associated with greater tau deposition in the medial parietal lobe. Medial parietal tau was not associated with functional connectivity between other regions, such as the hippocampus and the superior frontal gyrus. They also showed that the relationship between tau deposition in the medial parietal lobe and hippocampal-retrosplenial functional connectivity was unique to these regions.
Higher medial parietal tau was related to greater tau deposition in the MTL as well as increased global amyloid-beta levels. Individuals with greater functional connectivity between the hippocampus and retrosplenial cortex showed stronger correlations between tau levels in the MTL and medial parietal lobe. Interestingly, these individuals were also likely to have worse visuospatial episodic memory, which is in line with the role of the medial parietal lobe in representing visuospatial information. Thus, visuospatial episodic memory suffered when tau levels and functional connectivity between the MTL and medial parietal lobe were both high.
What's the impact?
The results of this study suggest that tau might spread between regions that are functionally connected to each other. Tau pathology in cognitively healthy individuals might be a potential biomarker for the development of Alzheimer’s disease, a notion that is supported by the current finding that visuospatial memory was lower only in individuals who showed a stronger association between tau accumulation and functional connectivity. Overall, these findings provide an exciting avenue for future research to use tau and functional connectivity in conjunction to track and predict the trajectory of cognitive decline.
Ziontz et al. Hippocampal connectivity with retrosplenial cortex is linked to neocortical tau accumulation and memory function. The Journal of Neuroscience (2021). Access the original scientific publication here.