Alzheimer’s of Central Alabama
Lindy Harrell Pre Doctoral Scholars in Alzheimer’s Disease Research
UAB Department of Neurology
2024
ACA’s Jr. Board is funding our 7th Lindy Harrell Pre-Doctoral Scholar in Alzheimer’s research in the UAB Department of Neurology, for a total of contribution of $300,000, since 2019. The Jr. Board, established in 2015, has attracted a dynamic group of young people who are ambitiously raising money with the goal of recruiting the brightest, most promising students to establish careers in Alzheimer’s research.
ACA has a long history of supporting research. From 2001-2017, ACA funded 24 research grants at Alabama universities that resulted in over $2.3 million in additional funding for continued study at UAB. In 2021, as part of ACA’s 30th Anniversary celebration, the Board of Directors established the Lindy Harrell Pre Doctoral Scholars Program in Alzheimer’s research at UAB.
We are proud to honor Dr. Lindy Harrell’s legacy by supporting student research. Dr. Harrell joined the UAB faculty in 1983 as the fourth member of the Department of Neurology and established a thriving program of research and clinical care in Alzheimer’s disease and related dementias. The same year ACA was founded (1991), the UAB Alzheimer’s Disease Center (ADC) was chartered by the Board of Trustees, with Dr. Lindy Harrell as the founding director. She led the ADC until 2005 and retired in 2013, when she was appointed Professor Emeritus by UAB. After retirement she became Board Certified in Addition Medicine and served as Medical Director at Bradford Health Services. Dr. Harrell has been a part of ACA since its inception and made the first donation to ACA which was used to publish our first newsletter. She continues to serve as ACA’s Vice President of Research.
ACA’s Scholars who have receive a total of $50,000 in scholarship funding include:
Samira Ramshe a graduate student in Dr. Rita Cowell’s lab, is our 2024-2025 scholar. She is working on potential strategies to protect brain cells from dysfunction and death by activating the function of lysosomes, the recycling centers of the cell that clean up cellular debris. This may have relevance to both AD and FTD (maybe even other neurodegenerative diseases).
Swetha Ravichandran, a Vision Science Graduate Program student at the University of Alabama at Birmingham School of Optometry, is our 2023-2024 scholar. Ravichandran, who is involved with Alzheimer’s disease research, says more can be done to help neurodegeneration, especially as society experiences increased life expectancy. “Having watched my grandfather battle Alzheimer’s disease further stirred my longing to tread toward this journey. As a doctoral student, I am now focused on exploring novel ocular biomarkers that could help in the diagnosis of preclinical neurological conditions like Alzheimer’s disease. Further, I wish to address major gaps in the field of ocular diagnostics and biomarkers to help the society through the application of my research findings.”
Tabea Soelter was our 2023 scholar. Tabea is a PhD student in the Genetics, Genomics and Bioinformatics theme within the UAB Graduate Biomedical Sciences program. She has a B.S. in Cell and Molecular Biology from Piedmont University. Tabea is currently investigating the cell-type-specific role of cell-cell communication between neuronal and non-neuronal cell populations in Alzheimer’s disease using public human data. She is also interested in the effects of aging on the Alzheimer’s disease brain and therefore employs wet-lab and computational approaches to understand age-associated changes in cell-cell communication using her own mouse sequencing data across multiple timepoints.
Ian Acton Matthews was our 2022 scholar. His primary research goal is to give credence to a more “holistic” idea of brain health, specifically that Alzheimer’s is a disease of the entire body rather than a dysfunction that stops at the neck. Though the medical community has known for years that exercise is protective for Alzheimer’s Disease (AD), it is not a feasible prescription for many that suffer from the worst the disease has to offer. Ian’s hypothesis centers on the signal that comes from muscles during exercise that tells the brain to both make new neurons and get rid of the build-up of toxic proteins. To test his theory, he has changed the muscle genes of a mouse so that their brain exhibits many of the benefits of exercise despite living a sedentary lifestyle. Ian believes he can mimic the benefits of exercise with genetics alone! Ian will compare the disease progression of 3 groups: a sedentary mouse-model for AD, the same AD mice running on wheels, and AD mice cross-bred with the “exercise-mimetic” mice. Ian hopes to see similar benefits in the model as the mice that are exercising.
Hunter Dean was our 2021 – 2022 scholar and worked in Dr. Erik Roberson’s lab. His project is “The Role of Allostery in Signaling Through the Alzheimer’s Disease–Associated Protein TREM2.”
Long version:
Alzheimer’s disease (AD) is the leading cause of dementia worldwide and the risk of developing AD is tripled by genetic variants in the immune receptor TREM2 or its binding partner ApoE. However, because multiple different kinds of immune responses can be triggered through TREM2, drugs that are currently in clinical trials to target TREM2 may be unintentionally activating immune responses that exacerbate AD, rather than treating it. We use computer simulations and cells cultured from mice to identify molecules that bind and activate TREM2 and determine how this activation is affected by AD-associated genetic variants. By better understanding TREM2’s binding mechanisms, we can begin to understand how genetic variants in and binding partners of TREM2 contribute to its role in disease and to develop drugs that more carefully target TREM2 as a treatment for AD and other neurodegenerative diseases.
Short version:
We use a mix of computer simulations and immune cells from mice to better understand how the genetic risk factor for Alzheimer’s disease TREM2 carries molecular signals in disease.
Nolwazi Gcwensa, was our 2020- 2021 Scholar and will be working in Laura Volpicelli’s lab in the Department of Neurology. Nolwazi’s project will determine how Lewy pathology could contribute to loss of synapses in the amygdala, neuronal dysfunction and how blocking immune cell activation in the brain may prevent synapse loss. Over 50% of AD patients have Lewy pathology, in addition to plaques and tangles, in the brain. Lewy pathology, which is associated with more severe symptoms of dementia and shorter lifespan, is found in the amygdala and may contribute to psychiatric symptoms in AD such as anxiety and fear.
Ashleigh Irwin was our 2019 -2020 Scholar and is in the Medical Scientist Training Program (MD/PhD), in Farah Lubin’s lab in the Department of Neurobiology. Her study is, “Manipulation of astrocytic DNA methylation in a mouse model of Alzheimer’s disease.” Amyloid plaques are a well-known feature of Alzheimer’s disease, however treatments targeting amyloid have been largely unsuccessful. While levels of amyloid in the brain stabilize early in the course of disease, the abnormal function of cells called astrocytes increases with disease progression. This suggests that aberrant astrocyte function may contribute to the progressive cognitive decline seen in patients with Alzheimer’s disease. Irwin hypothesizes that changes in astrocyte epigenetics, or the modifications to DNA that can turn genes off or on, drives abnormal astrocyte function and contributes to impaired memory. In addition to determining differences in DNA modifications in astrocytes, she proposes to manipulate these modifications at specific memory related genes in order to restore cognitive function in a model of Alzheimer’s disease. If successful, this project provides the foundation for novel epigenetic therapies.