Tau deposition is associated with functional isolation of the hippocampus in aging

Area of Science:

• Neuroscience
• Neurodegenerative Diseases
• Medical Imaging

Background:

• Tau protein aggregation is implicated in aging and Alzheimer's disease (AD).
• Tau pathology may cause memory loss by disrupting medial temporal lobe (MTL)-dependent memory systems.
• Episodic memory decline is a hallmark of cognitive aging and AD.

Purpose of the Study:

• To investigate tau-mediated mechanisms of hippocampal dysfunction in episodic memory decline.
• To examine the relationship between tau burden, functional connectivity, and memory performance.

Main Methods:

• Functional magnetic resonance imaging (fMRI) to measure hippocampal regional homogeneity (ReHo) and functional connectivity.
• Positron emission tomography (PET) with tau-specific tracers to quantify tau pathology.
• Correlation analyses between tau burden, ReHo, functional connectivity, and memory performance.

Main Results:

• Age and tau pathology were associated with increased hippocampal ReHo.
• Functional disconnection between the hippocampus and anterior-temporal object memory network correlated with higher hippocampal ReHo and tau burden.
• These associations were not observed in the posteromedial context/spatial network.
• Higher hippocampal ReHo predicted worse memory performance.

Conclusions:

• Tau pathology contributes to hippocampal dysfunction by disconnecting it from specific MTL memory systems.
• This disconnection leads to increased local hippocampal coherence and subsequent memory decline.
• Findings highlight tau's role in age-related and AD-associated memory impairment.