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Title: Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.
Authors:
ORCiD logo [1] ;  [2] ;  [1] ;  [2]
  1. Univ. of California, Berkeley, CA (United States)
  2. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Accepted Manuscript
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1379725

Leal, Stephanie L., Landau, Susan M., Bell, Rachel K., and Jagust, William J.. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline. United States: N. p., Web. doi:10.7554/eLife.22978.
Leal, Stephanie L., Landau, Susan M., Bell, Rachel K., & Jagust, William J.. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline. United States. doi:10.7554/eLife.22978.
Leal, Stephanie L., Landau, Susan M., Bell, Rachel K., and Jagust, William J.. 2017. "Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline". United States. doi:10.7554/eLife.22978. https://www.osti.gov/servlets/purl/1379725.
@article{osti_1379725,
title = {Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline},
author = {Leal, Stephanie L. and Landau, Susan M. and Bell, Rachel K. and Jagust, William J.},
abstractNote = {The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.},
doi = {10.7554/eLife.22978},
journal = {eLife},
number = ,
volume = 6,
place = {United States},
year = {2017},
month = {2}
}