TY  - JOUR
AU  - Harrison, Theresa M
AU  - Maaß, Anne
AU  - Adams, Jenna N
AU  - Du, Richard
AU  - Baker, Suzanne L
AU  - Jagust, William J
TI  - Tau deposition is associated with functional isolation of the hippocampus in aging.
JO  - Nature Communications
VL  - 10
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-07924
SP  - 4900
PY  - 2019
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Aging: metabolism
KW  - Aging: physiology
KW  - Aging: psychology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: physiopathology
KW  - Alzheimer Disease: psychology
KW  - Amyloid beta-Peptides: metabolism
KW  - Aniline Compounds
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Brain: physiopathology
KW  - Carbolines
KW  - Cognitive Aging: physiology
KW  - Cognitive Aging: psychology
KW  - Contrast Media
KW  - Entorhinal Cortex: diagnostic imaging
KW  - Entorhinal Cortex: metabolism
KW  - Entorhinal Cortex: physiopathology
KW  - Executive Function
KW  - Female
KW  - Functional Neuroimaging
KW  - Hippocampus: diagnostic imaging
KW  - Hippocampus: metabolism
KW  - Hippocampus: physiopathology
KW  - Humans
KW  - Male
KW  - Memory, Episodic
KW  - Memory, Short-Term
KW  - Middle Aged
KW  - Neural Pathways: diagnostic imaging
KW  - Neural Pathways: metabolism
KW  - Neural Pathways: physiopathology
KW  - Neurofibrillary Tangles: metabolism
KW  - Positron-Emission Tomography
KW  - Temporal Lobe: diagnostic imaging
KW  - Temporal Lobe: metabolism
KW  - Temporal Lobe: physiology
KW  - Thiazoles
KW  - Young Adult
KW  - tau Proteins: metabolism
KW  - 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Aniline Compounds (NLM Chemicals)
KW  - Carbolines (NLM Chemicals)
KW  - Contrast Media (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
KW  - Thiazoles (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31653847
C2  - pmc:PMC6814780
DO  - DOI:10.1038/s41467-019-12921-z
UR  - https://pub.dzne.de/record/141600
ER  -