# Effect of hippocampal tau pathology on CA1 function and memory processing in aging

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $67,174

## Abstract

PROJECT SUMMARY
In both aging and Alzheimer's disease (AD), hyperphosphorylated forms of the tau protein preferentially
develop within the CA1 subfield of the hippocampus. The hippocampus is critical to normal memory function,
and thus tau deposition within CA1 may lead to age- and disease-related memory decline. However, the
contribution of hippocampal tau to CA1 dysfunction and behavioral expression of memory impairment has not
previously been investigated. The current study aims to determine the effects of hippocampal tau pathology on
CA1 activation and behavioral performance during memory using a multimodal neuroimaging approach in
cognitively normal older adults. Tau pathology will be measured with positron emission tomography (PET) and
the novel second-generation tau-PET tracer [18F] MK-6240, which enables reliable quantification of
hippocampal tau-PET signal for the first time. We will use functional magnetic resonance imaging (fMRI) to
assess CA1 activation during memory processing. Recent studies have proposed that CA1 specifically
supports statistical learning, a type of memory in which regularities between experiences are learned. Older
adults will thus perform a statistical learning task during fMRI acquisition to derive measures of CA1 activation
and statistical learning behavioral performance. We will also measure amyloid-β with [18F] Florbetapir PET
and CA1 volume with structural MRI to explore the additional contribution of these factors. In Aim 1, we will
determine the relationship between statistical learning behavioral performance and CA1 activation in aging by
comparing activation between high- and low-performing older adults, and modeling activation changes across
the task. In Aim 2, we will identify how tau pathology within the hippocampus is related to both CA1 activation
and statistical learning behavioral performance. Finally, in Aim 3, we will measure functional connectivity
between hippocampal subfields and the entorhinal cortex during the statistical learning task, and determine the
effects of tau pathology on this connectivity. Findings from this study will help elucidate the role of hippocampal
tau pathology on age- and disease-related memory decline. Additionally, behavioral performance on statistical
learning tasks may emerge as a sensitive biomarker for early hippocampal tau pathology. Completion of the
proposed research will directly support the applicant's training goals, including (1) fMRI experimental design
and advanced analysis, (2) additional PET training with new tracers and high-resolution quantification, (3)
conceptual development in cognitive neuroscience of memory, and (4) growth of skills to support an academic
career. The University of California, Irvine provides a network of innovative cognitive neuroscience and
Alzheimer's researchers with world-class facilities for neuroimaging. Dr. Michael Yassa, the sponsor, is a
leader in studying age-related memory decline with multimodal neuroimaging. The com...

## Key facts

- **NIH application ID:** 10516028
- **Project number:** 5F32AG074621-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Jenna Nicole Adams
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516028

## Citation

> US National Institutes of Health, RePORTER application 10516028, Effect of hippocampal tau pathology on CA1 function and memory processing in aging (5F32AG074621-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10516028. Licensed CC0.

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