# Neural mechanisms of social attachment disruption in frontotemporal dementia

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $169,020

## Abstract

PROJECT SUMMARY/ABSTRACT
Social cognition, and social attachment in particular, is often significantly disrupted in age-related
neuropsychiatric disease. Frontotemporal dementia (FTD) is characterized by disruptions in social attachment
behavior and loss of empathy early in the course of the disease. We currently lack a mechanistic understanding
of the neurobiology of attachment behavior or its disruption in disease and have no interventions for these
profoundly impairing symptoms, despite their potential as early diagnostic and therapeutic targets. The candidate
for this K08 Mentored Career Development Award is a physician scientist and psychiatrist at the University of
California, San Francisco. Her long-term career goal is to understand the impact of aging and neurodegenerative
disease on the neurobiology of social behavior. The overall objective of the proposed research plan is to elucidate
the molecular and neural circuit pathways mediating social attachment changes in FTD. The candidate proposes
to use the prairie vole, a unique model organism that forms long-term adult pair bonds, to understand the
neurobiology of social attachment. In her preliminary work, she has used molecular genetic tools to knock out
progranulin (Grn), one of the most common genetic causes of FTD, in the vole. This work represents an
innovative and novel approach to studying attachment deficits in dementia. She proposes to first examine the
effects of loss of genes relevant to social behavior and to FTD, the oxytocin receptor (OxtR) and Grn, using both
behavioral and transcriptomic profiling with age. She will then test the hypothesis that loss of OxtR and Grn
converge on specific neural circuits responsible for the presentation of social deficits, using in vivo calcium
imaging and viral tracing methods to map patterns of neural activity and connectivity. The proposed research is
significant because it seeks to mechanistically link the risk genes associated with neurodegenerative disease to
the neural circuit changes and social attachment disruptions characteristic of these diseases. This proposal
presents a five-year research career development program designed to provide a foundation for an independent
research program. The specific career development goals outlined in this application include training in systems
neuroscience, advanced sequencing and bioinformatics methods, and in translational neurodegenerative
disease research. These skills build on the candidate's prior experience in neuroendocrine signaling and its role
in aging biology and neurodegenerative disease. The primary mentorship team (Drs. Manoli, Miller, and
Ingraham) has expertise in molecular genetics, systems neurophysiology, and translational FTD research. Other
key contributors and collaborators provide expertise in vole behavior (Dr. Bales), transcriptomics and
bioinformatics (Dr. Willsey), and comparative genomics (Dr. Yokoyama). The direct training in research
methodology and career support ...

## Key facts

- **NIH application ID:** 10841679
- **Project number:** 5K08AG070377-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Kristen Berendzen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $169,020
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841679

## Citation

> US National Institutes of Health, RePORTER application 10841679, Neural mechanisms of social attachment disruption in frontotemporal dementia (5K08AG070377-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10841679. Licensed CC0.

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