Journal Article

DZNE-2020-07924

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tau deposition is associated with functional isolation of the hippocampus in aging.

Harrison, T. M. (Corresponding author) ; Maaß, A.DZNE* ; Adams, J. N. ; Du, R. ; Baker, S. L. ; Jagust, W. J.

2019
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-019-12921-z

Abstract: The tau protein aggregates in aging and Alzheimer disease and may lead to memory loss through disruption of medial temporal lobe (MTL)-dependent memory systems. Here, we investigated tau-mediated mechanisms of hippocampal dysfunction that underlie the expression of episodic memory decline using fMRI measures of hippocampal local coherence (regional homogeneity; ReHo), distant functional connectivity and tau-PET. We show that age and tau pathology are related to higher hippocampal ReHo. Functional disconnection between the hippocampus and other components of the MTL memory system, particularly an anterior-temporal network specialized for object memory, is also associated with higher hippocampal ReHo and greater tau burden in anterior-temporal regions. These associations are not observed in the posteromedial network, specialized for context/spatial information. Higher hippocampal ReHo predicts worse memory performance. These findings suggest that tau pathology plays a role in disconnecting the hippocampus from specific MTL memory systems leading to increased local coherence and memory decline.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Aging: metabolism (MeSH) ; Aging: physiology (MeSH) ; Aging: psychology (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: physiopathology (MeSH) ; Alzheimer Disease: psychology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Aniline Compounds (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Brain: physiopathology (MeSH) ; Carbolines (MeSH) ; Cognitive Aging: physiology (MeSH) ; Cognitive Aging: psychology (MeSH) ; Contrast Media (MeSH) ; Entorhinal Cortex: diagnostic imaging (MeSH) ; Entorhinal Cortex: metabolism (MeSH) ; Entorhinal Cortex: physiopathology (MeSH) ; Executive Function (MeSH) ; Female (MeSH) ; Functional Neuroimaging (MeSH) ; Hippocampus: diagnostic imaging (MeSH) ; Hippocampus: metabolism (MeSH) ; Hippocampus: physiopathology (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Memory, Episodic (MeSH) ; Memory, Short-Term (MeSH) ; Middle Aged (MeSH) ; Neural Pathways: diagnostic imaging (MeSH) ; Neural Pathways: metabolism (MeSH) ; Neural Pathways: physiopathology (MeSH) ; Neurofibrillary Tangles: metabolism (MeSH) ; Positron-Emission Tomography (MeSH) ; Temporal Lobe: diagnostic imaging (MeSH) ; Temporal Lobe: metabolism (MeSH) ; Temporal Lobe: physiology (MeSH) ; Thiazoles (MeSH) ; Young Adult (MeSH) ; tau Proteins: metabolism (MeSH) ; 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole ; Amyloid beta-Peptides ; Aniline Compounds ; Carbolines ; Contrast Media ; MAPT protein, human ; Thiazoles ; tau Proteins ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

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Contributing Institute(s):

1. Clinical Neurophysiology and Memory (AG Düzel)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2019

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