# Effect of beta-amyloid and tau pathology on functional network organization and memory in aging

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $67,582

## Abstract

Project Summary
The goal of the proposed research is to investigate a potential mechanism by which the accumulation of beta
amyloid (Aβ) plaques and tau tangles could lead to episodic memory impairments. A loss of episodic memory is
one of the hallmarks of age-related cognitive decline and is a major risk factor for dementia. Before the symptoms
of dementia occur in Alzheimer’s disease (AD), Aβ plaques and neurofibrillary tau tangles begin to appear in the
brain. This process typically starts in the neural systems associated with episodic memory and tracks closely
with age-related memory impairments. An important open question is how Aβ and tau accumulation lead to
memory decline. One possibility is that Aβ and tau may lead to memory loss through the disruption, or
‘dedifferentiation’, of episodic memory networks. For example, large-scale canonical networks, such as the
default mode, salience, and attention networks, have been reported to be less segregated in older vs. younger
adults, and such dedifferentiation has been associated with impaired performance on a variety of tasks.
However, the molecular and pathological substrate of these observations is unknown. I propose to test whether
the accumulation of Aβ and tau is associated with network segregation in the episodic memory system and
whether network segregation mediates the association between neuropathology and memory decline. In
preliminary analyses, I used resting state fMRI to measure functional network segregation in the neural systems
most associated with episodic memory (the anterior temporal (AT) and posteromedial (PM) networks) in older
and younger adults. I found that the AT and PM networks were significantly less segregated in older relative to
younger adults. Building on these findings, I will study older adults with Aβ and tau PET at baseline, and memory
performance at three time points over a period of about 6 years. My proposed research will test the following
hypotheses: (1) Increased Aβ/tau will be associated with less segregated AT/PM networks, (2) less segregated
AT/PM networks will predict worse episodic memory performance at baseline as well as change in performance
over time, and (3) more Aβ/tau will predict worse memory performance (at baseline and change in performance
over time), and network segregation will mediate the relationship between Aβ/tau and performance. Together,
the proposed experiments will test a model in which age-related increases in Aβ and tau lead to neural
dedifferentiation of intrinsic functional memory networks, which in turn leads to memory deficits. By studying this
episodic memory system in healthy older adults, we can advance our understanding of healthy aging and its
similarities to and differences from pathological aging, which could serve as a crucial building block for the early
detection of AD.

## Key facts

- **NIH application ID:** 10368050
- **Project number:** 5F32AG067657-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Kaitlin Elizabeth Cassady
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-08-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368050

## Citation

> US National Institutes of Health, RePORTER application 10368050, Effect of beta-amyloid and tau pathology on functional network organization and memory in aging (5F32AG067657-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10368050. Licensed CC0.

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