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Title: Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

Abstract

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]
  1. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging
  3. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1393136
DOE Contract Number:  
AC02-05CH11231; F31-AG049564; R01-AG034570
Resource Type:
Journal Article
Journal Name:
Journal of Neuroscience
Additional Journal Information:
Journal Volume: 37; Journal Issue: 12; Journal ID: ISSN 0270-6474
Publisher:
Society for Neuroscience
Country of Publication:
United States
Language:
English
Subject:
amyloid; episodic memory; fMRI; hippocampus; PET; tau

Citation Formats

Marks, Shawn M., Lockhart, Samuel N., Baker, Suzanne L., and Jagust, William J. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging. United States: N. p., 2017. Web. doi:10.1523/JNEUROSCI.3769-16.2017.
Marks, Shawn M., Lockhart, Samuel N., Baker, Suzanne L., & Jagust, William J. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging. United States. doi:10.1523/JNEUROSCI.3769-16.2017.
Marks, Shawn M., Lockhart, Samuel N., Baker, Suzanne L., and Jagust, William J. Wed . "Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging". United States. doi:10.1523/JNEUROSCI.3769-16.2017.
@article{osti_1393136,
title = {Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging},
author = {Marks, Shawn M. and Lockhart, Samuel N. and Baker, Suzanne L. and Jagust, William J.},
abstractNote = {Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.},
doi = {10.1523/JNEUROSCI.3769-16.2017},
journal = {Journal of Neuroscience},
issn = {0270-6474},
number = 12,
volume = 37,
place = {United States},
year = {2017},
month = {3}
}