Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

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Abstract

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.

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Stephanie L Leal

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States

For correspondence
stephanieleal@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8082-8291
Susan M Landau

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Rachel K Bell

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
William J Jagust

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States

For correspondence
jagust@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

Funding

National Institute on Aging (AG054116)

Stephanie L Leal

National Institute on Aging (AG034570)

William J Jagust

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Informed consent was obtained from all research participants and approved by the Institutional Review Boards of Lawrence Berkeley National Labs and UC Berkeley.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.