‘New Horizons in Alzheimer’s Disease and Related Dementias’ Awardees
In recognition of the quality of Alzheimer’s disease and related dementias (ADRD) research being conducted at 91, the , the College of Engineering and Computer Science, the Institute for Human Health and Disease Intervention (I-Health), the 91 Stiles-Nicholson Brain Institute, and the David and Lynn Nicholson Center for Neurodegenerative Disease Research recently formed a collaboration to establish the “New Horizons in Alzheimer’s Disease and Related Dementias (ADRD)” Pilot Funding Program.
“By establishing this new pilot program, we are tapping into an incredible breadth of ‘brain’ power and expertise throughout many disciplines across 91,” said Randy Blakely, Ph.D., executive director, 91 Stiles-Nicholson Brain Institute, the David J.S. Nicholson Distinguished Professor in Neuroscience, and a professor in the Department of Biomedical Science in 91’s Schmidt College of Medicine. “Our goal is to seed new transformative advancements in interdisciplinary research into the origins, diagnosis and treatment of Alzheimer’s disease and related dementias. Specifically, these investments will support efforts of the winning teams to obtain critical preliminary data needed to obtain extramural funding that can lead to truly transformative research.”
In late 2022, a one-day symposium with plenary speakers and panels brought together ADRD researchers from both within and outside the university, subsequently leading to this university-wide pilot funding competition.
“Alzheimer’s disease is the most common form of dementia and age-related neurodegenerative diseases. In the United States, about 40 percent of the population will experience Alzheimer's disease at age 85, and that number is projected to reach 15 million by 2050,” said , Ph.D., executive director, 91 I-Health and a professor in the in 91’s . “The innovative and interdisciplinary pilot projects that have been funded by this new program have important implications not only for Alzheimer’s disease, but for dementia and cognitive impairment, which have a much broader reach among the geriatric population.”
The three pilot awards selected for funding are:
“Contribution of HTRA1 and MT5-MMP to the Impact of Hereditary Alzheimer’s Disease Mutations” ($37,500) awarded to Hongjie Wang, Ph.D., an assistant research professor in the Department of Chemistry and Biochemistry, 91 Charles E. Schmidt College of Science and a member of 91’s I-Health and Stiles-Nicholson Brain Institute; and Ning Quan , Ph.D., a professor of biomedical science, 91 Schmidt College of Medicine and a member of the 91 Stiles-Nicholson Brain Institute.
The major defining pathological hallmarks of AD are the intracellular neurofibrillary tangles from heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolytic cleavage of amyloid precursor protein (APP). Although AD is widely accepted to be a disease of the cerebral gray matter, several pathological changes have been noted in the white matter, including the loss of axons, oligodendrocytes and reactive astrocytosis. Demyelination of the white matter is reported to occur prior to the presence of Aβ plaques and neurofibrillary tangles in the presymptomatic stages of AD.
This study will generate data about the role HTRA1, a gene that provides instructions for making a protein found in many of the body’s organs and tissues, in APP processing, oligodendrocyte precursor cell (OPC) differentiation and disease-associated oligodendrocytes (DOL) function. Results from this work will increase the understanding of the role of HTRA1 in the full picture of AD pathology. Whether HTRA1 expression is one of the factors in regulating AD-DOL generation or is a passive gene signature for AD-DOL remains an open question. Data from this research will provide a preliminary answer for its role in DOL function.
“Early Prediction of Alzheimer's Disease and Related Dementias (ADRD) on Preclinical Assessment Data Using Machine Learning (ML) Tools” ($37,500) awarded to , DNP, APRN, associate dean of clinical practice, professor and director of the , 91 Christine E. Lynn College of Nursing; , Ph.D., an associate professor, Department of Psychology, 91 Charles E. Schmidt College of Science and associate director of the 91 Center for Future Mind; and , Ph.D., dean; , Ph.D., associate professor and statistician; and , Ph.D., senior research fellow, all within 91’s Christine E. Lynn College of Nursing; and Ph.D. student Subhosit Ray, Department of Psychology, 91 Charles E. Schmidt College of Science.
Researchers will explore early diagnosis and discovery of AD risk-associated markers from the statistical inference of medical records and medical history. This novel study will use evidence-based aims, advanced statistical, data science methods, artificial intelligence/machine learning, and large-scale patient data to develop and test robust models to predict the early stages of AD.
The study will assess the most effective clinical management for patients with ADRD, including early diagnosis, delay in the onset, and slow progression of these diseases. Available therapies aim to improve patients’ and caregivers’ quality of life by delaying the progression and managing symptoms. These include respite, psychotherapeutics, psychoeducation, counseling and support groups. As there is no direct cure for the disease, a better assessment of the disease prognosis can significantly help the patient and family plan and better manage the risk factors associated with ADRD.
“As a college dedicated to caring as well as advancing science, this project, spearheaded by Dr. Ortega will provide another important tool to enhance the incredible programs and services offered in our Louis and Anne Green Memory and Wellness Center,” said , Ph.D., associate dean for research and Schmidt Distinguished Professor in 91’s Christine E. Lynn College of Nursing, and a faculty fellow of 91 I-Health. “Importantly, results from this research will not only help to improve the quality of life for those with Alzheimer’s disease and related dementias, it also will help the more than 11 million family members and other caregivers nationwide who provide unpaid care for their loved ones.”
“Alzheimer’s Early Detection Via Noninvasive Analysis of Retinal Vascular Dynamics” ($25,000) awarded to Ramin Pashaie , Ph.D., associate professor in the Department of Electrical Engineering and Computer Science and a fellow, 91 Institute for Sensing and Embedded Network Systems Engineering (I-SENSE) within the College of Engineering and Computer Science; and , Ed.D., Christine E. Lynn Eminent Scholar and professor, 91 Christine E. Lynn College of Nursing.
In clinical practice, AD is diagnosed using magnetic resonance imaging (MRI) or positron emission tomography (PET) looking for signs of structural or metabolic alterations in the brain. Despite obvious benefits of imaging techniques for disease diagnosis, these methods are neither cost effective nor accessible to large populations, and are not yet fully prognosis capable. Brain alterations in AD are commonly accompanied by ocular impairments, and presence of the disease in the eye often parallels that of the brain. Since the eye is accessible for imaging, several procedures have been proposed for the detection of AD via retinal imaging.
In this study, researchers will determine the potential use of non-invasive retinal imaging as a clinically viable and cost-effective procedure for AD screening. They will test the potential of two new retinal hemodynamic features for early detection of AD and will evaluate the feasibility and reliability of using these two features to estimate the state of the disease in the brain from the data collected non-invasively in the retina.
Additionally, researchers will use the same instrumentation to measure changes in retinal structure and vascular morphology as complementary features to improve the precision of their computer-based disease state estimation algorithms. If successful, this research will lead to the clinical translation of the technology where AD diagnosis is done through a set of fully automated retinal imagining tests.
“The eyes are not just the window to the soul, they also provide a unique glimpse into diseases of the brain such as Alzheimer’s,” said Stella Batalama, Ph.D., dean, 91 College of Engineering and Computer Science. “Spearheaded by the team of Dr. Pashaie, an expert in optics and photonics and their applications in neuroscience, and Dr. Tappen, an experienced clinical researcher with expertise in aging and dementia research, this study will provide a novel approach for a noninvasive way to detect diseases of the brain utilizing ophthalmological examinations. This work has the potential to provide a more cost-effective and accessible tool for diagnosing Alzheimer’s disease and other related dementias.”
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