(SACRAMENTO)
At the heart of every research initiative lies a deeply personal motivation, a quest for understanding that drives individuals like UC Davis neuropathology expert Brittany Dugger. Her inspiration stemmed from the contrasting ways dementia impacted her two grandmothers, leaving her grappling with unanswered questions about their diverse behaviors under the same diagnosis.
Dugger is a neuropathology expert at UC Davis
“My grandmothers had dementia at the same time, but their diseases manifested in starkly different ways. I remember feeling frustrated and confused. How is it possible for them to share the same diagnosis when their behaviors are worlds apart? I was determined to find answers,” Dugger recounted.
Currently, Dugger serves as an associate professor in the Department of Pathology and Laboratory Medicine and spearheads the Neuropathology Core at the UC Davis Alzheimer’s Disease Center, where she channels her expertise into groundbreaking research.
In 2019, she successfully secured a substantial $3.8 million, five-year grant from the National Institute on Aging (NIA). This funding initiated the first large-scale effort aimed at comprehensively describing the neurological manifestations of Alzheimer’s disease among individuals of Mexican, Cuban, Puerto Rican, and Dominican descent.
The new grant fosters collaboration among researchers from diverse fields and institutions, with a focus on understanding how Hispanic heritage influences the pathological, demographic, and clinical characteristics of Alzheimer’s disease.
Moreover, the grant integrates innovative techniques such as machine learning, citizen science, and precision medicine, particularly to address the needs of Hispanic and Latino communities affected by Alzheimer’s.
Engaging people with Alzheimer’s through gaming
In a recent pilot study, Dugger and her team developed and tested an interactive game called Beta Catchers. This initiative is in collaboration with the Human Computation Institute, an organization dedicated to creating online platforms that enable public volunteers to analyze scientific data through gamification.
A slide with a stained sample of brain tissue
“We have over 80,000 registered users from 200 countries who collaboratively analyze scientific data. This collective effort significantly accelerates research,” explained Pietro Michelucci, executive director of the Human Computation Institute.
Beta Catchers is specifically designed to engage individuals identifying as Hispanic or Latino. In this game, players evaluate stained images of human brain tissues to identify and trace the pathologies associated with Alzheimer’s disease, including amyloid plaques and neurofibrillary tangles.
“Relying on a single non-expert individual isn’t sufficient for analysis. Our approach combines assessments from multiple people, which enhances accuracy and mimics expert-level answers,” Michelucci elaborated.
The team has developed an advanced algorithm that leverages the wisdom of the crowd to yield high-quality results in pathology classification. With the new grant, there are plans to further refine and enhance this algorithm.
“How do we interpret the varied responses from our players? That aspect of our work is immensely rewarding, as we aim to answer significant research questions through human computation. We’ve uncovered the incredible potential of the ‘crowd effect’ in tackling the complex task of classifying these toxic plaques,” Michelucci stated.
The researchers aspire to include individuals with Alzheimer’s, along with their families, in the gaming experience. Set to launch in summer 2025, the new platform will be available in both English and Spanish.
In addition to expanding the dataset for dementia pathologies, the game offers valuable outreach and educational opportunities to participants.
Disease evaluation for precision medicine
One important task is identifying plaque in brain tissues
Another crucial component of Dugger’s new grant focuses on the evaluation of Alzheimer’s disease. She will explore the methodologies scientists use to assess its pathologies and their implications for clinical practice.
“The way we evaluate diseases profoundly impacts our understanding of their pathology and treatment. Is the assessment binary—present or absent? Or do we employ a spectrum including non, mild, moderate, and severe ratings? Our evaluative approach directly influences diagnoses,” Dugger explained.
Drawing a parallel to cancer assessment, she noted that cancer severity and grade level inform treatment decisions. Conversely, this level of nuanced classification is still largely absent in dementia research. Enhanced phenotyping of the disease could greatly benefit precision medicine efforts.
Precision medicine research examines the influence of social and demographic factors on health disparities. It seeks to understand how neuropathology presents variably across diverse populations. The ultimate objective is to diminish health inequities and improve medical outcomes by ensuring that patients receive appropriate treatment tailored to their specific needs.
Dementia can manifest very differently in people
“Our research aims to bridge essential knowledge gaps in Alzheimer’s by delivering an objective quantitative understanding of the disease’s variances,” Dugger stated. “We will actively involve the community to investigate the neuropathologic landscape of Alzheimer’s, paving the way for enhanced precision medicine strategies, particularly for those in the Hispanic community.”
For this endeavor, Dugger collaborates with Chen-Nee Chuah, a UC Davis professor of electrical and computer engineering renowned for her expertise in data science, artificial intelligence (AI), and machine learning (ML). She will build upon her work with the UC-wide initiative known as UC Noyce Initiative, advancing the development of computer models that support precision medicine initiatives.
“In this project, we aim to tackle bias present in AI/ML models. A key strategy for achieving this is utilizing brain tissue images from diverse cohorts,” Chuah added.
Through a separate grant, the team will establish a comprehensive infrastructure designed to facilitate the sharing of pathology images nationwide, creating a digital slide archive akin to a searchable dictionary.
For more inclusive research on dementia
In their original grant proposal, Dugger and her team posed a vital question: Does dementia vary among individuals from different backgrounds?
Brittany Dugger choosing a sample from the UC Davis Alzheimer’s Disease Center’s brain bank
“Much of the research on dementia has centered on specific demographics,” Dugger noted. “It is crucial to investigate diverse populations, including those identifying as Hispanic, to discover cures that serve all segments of the population.”
The research team examined brain tissue samples from UC Davis, UC San Diego, and Columbia University’s national Alzheimer’s disease research centers. Their examination concentrated on the location and quantity of plaques associated with dementia in the brains of individuals with Alzheimer’s, enabling a comprehensive micro-examination of the affected areas.
“Instead of taking a broad view, we aimed for a detailed street-level perspective of the brain,” Dugger emphasized.
Their study demonstrated several commonalities among those with dementia; however, individuals who identified as Hispanic exhibited a higher prevalence of cerebrovascular disease alongside their Alzheimer’s condition.
“I take great pride in UC Davis being designated as a Hispanic Serving Institution. Our research is firmly aligned with the mission of supporting Hispanic communities and contributing to healthy aging,” Dugger expressed.
From left to right, profile pictures of Lorena Garcia, Laurel Alison Beckett, Dan Mungas, Chen-Nee Chuah, Luis Carvajal-Carmona and Paul Lott
Partnerships and Collaborations
Dugger’s grant entails the involvement of researchers with a wide range of expertise. Alongside Chuah and Michelucci, the collaboration includes associate professor David Gutman of Emory University and several UC Davis professors.
Dugger expressed immense gratitude for her collaborators and the participants who contribute to her research endeavors.
“Our work would not be possible without their invaluable data and samples. The citizen science element allows community members to engage actively in data analysis,” Dugger concluded.
The UC Davis Alzheimer’s Disease Center
The UC Davis Alzheimer’s Disease Center stands as one of only 33 research centers officially recognized by the National Institute on Aging. Located in both Sacramento and Walnut Creek, the center is dedicated to translating research findings into better diagnostic tools and treatments for dementia, with the overarching goal of discovering effective prevention and cures for Alzheimer’s disease. Additionally funded by the state of California, the center uniquely enables researchers to study the disease’s effects on a notably diverse population. For further information, visit ucdavis.edu/alzheimers/.
How is community engagement utilized in Dugger’s approach to Alzheimer’s disease research?
/p> and our commitment to serving the Hispanic community through research and outreach,” Dugger stated. “By focusing on these unique aspects of dementia in diverse populations, we hope to improve diagnostic accuracy and patient care for everyone affected by Alzheimer’s disease.”
Dugger’s work continues to break new ground in understanding how Alzheimer’s disease manifests differently across cultural and demographic lines. By leveraging community engagement, innovative technologies, and interdisciplinary collaboration, she aims to reshape the future of dementia research and treatment, ultimately fostering a more inclusive approach to studying and addressing this pervasive disease.
