In this month’s ANA Q&A, we spoke with Tania Torbati, BSc, a student at Western University of Health Science in the College of Osteopathic Medicine of the Pacific and a Neurology & Neurosurgery Research Intern at Cedars-Sinai. Torbati talked about her work on early diagnosis and immune-based therapies for Alzheimer’s disease, her research as an intern for the Koronyo-Hamaoui Research Lab, and how the ANA has helped her grow as a Student Member.
What does the public need to understand about Alzheimer's disease?
Alzheimer’s disease is the most common form of dementia, typified by neurofibrillary tangles, age-dependent amyloid-beta (Aβ) accumulation, cerebral inflammation, synaptic loss, and fatal neurodegeneration. Unfortunately, the number of individuals with Alzheimer’s disease age 65 years and older is expected to reach 7.1 million by 2025, which is an almost 22% increase from those diagnosed with Alzheimer’s disease in 2020. Given that Alzheimer’s disease currently has no cure and most treatments only address symptom management, there is a paramount need for research directed toward reducing Alzheimer’s disease-related pathology and resultant symptomatology, as displayed by gradual memory loss and cognitive dysfunction. In addition, continued investigation on multimodal detection models for Alzheimer’s disease are critical as current detection often occurs at late symptomatic stages of the disease, when brain damage is too widespread and hallmark; neuropathologies such as cerebral Aβ burden have reached a plateau state and are subsequently less receptive to clearance.
My hope is that the public will come to understand that regardless of such disheartening statistics and disease factors, many recent and novel research investigations show great promise for the future of early Alzheimer’s disease detection and disease-modifying treatment. In particular, individuals in the general public may not know that early and specific signs of Alzheimer’s disease like Aβ accumulation are found in the eye’s retina, which is a central nervous system tissue like the brain but with the advantage of increased accessibility for direct, non-invasive retinal imaging.
As an undergraduate at UCLA and medical student at Western University of Health Sciences, I have received the most incredible mentorship from the members of the Koronyo-Hamaoui lab, led by Professor Maya Koronyo-Hamaoui, at Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Institute, chaired by Dr. Keith L. Black. Of note, our team was the first to demonstrate the existence of these hallmark signs in the retina of humans, by both histological examination and clinical trials with live patients. Co-mentored by Dr. Oana Dumitrascu of Mayo Clinic Arizona’s Neurology Department, I had the invaluable opportunity to analyze amyloid-beta plaques in retinal subregions of patients with mild cognitive impairment and Alzheimer’s disease.
How are treatment options for Alzheimer's disease different today versus 10 years ago?
Treatment options for Alzheimer’s disease are still very limited, and much more research is needed. One important advancement is the recent approval of Aducanumab, also known as Aduhelm, which is the first FDA-approved drug that targets Alzheimer’s disease neuropathology and has been shown to decrease cerebral amyloid plaques in early stages of Alzheimer’s disease. Nevertheless, much more research is still required to help expand the treatment options available for Alzheimer’s disease patients.
What work is your lab undertaking to move understanding or treatment for Alzheimer's disease forward?
As a research intern in the Koronyo-Hamaoui lab for the past seven years, I have participated in multiple projects demonstrating that glatiramer acetate (GA) immunomodulation therapy curbs Alzheimer’s disease neuropathology in double-transgenic (ADtg) mouse models of the disease. Notably, GA immunization promoted recruitment of peripheral monocytes to the brain, prevented cognitive decline, and instigated central nervous system repair, as witnessed with markedly decreased cerebral GFAP-expressing reactive astrocytes and neuroinflammation, preservation of synaptic integrity, and reduced cerebral Aβ plaque burden. Overall, our studies have revealed that GA immunomodulation facilitates restoration of cerebral homeostasis in ADtg mice, setting the foundation to translate this novel therapeutic treatment to humans.
Also, our results illustrate the intimate interaction between the immune system and central nervous system as well as the neuroprotective benefits of boosting the innate immune response to upregulate the body’s inherent ability to self-repair.
My interest in the relationship between different body systems further sparked my recent research endeavors in Neuro-Ophthalmology and retinal amyloid imaging for early detection of Alzheimer’s disease. Current amyloid-PET brain imaging visualizes cerebral Aβ with limited accessibility and identifies advanced disease stages of Alzheimer’s disease when neuropathology is more aggressive and less responsive to removal. Given that the retina is the only central nervous system tissue not enclosed by bone, our team pioneered curcumin-labeled retinal autofluorescence imaging (RFI) to bypass the shielded brain and identified increased total and proximal mid-periphery (PMP) retinal amyloid count in patients with cognitive impairment, providing a topographic and quantitative assessment of retinal amyloid burden that previously remained poorly understood.
We also found that retinal Aβ count may predict hippocampal volume and cognitive scores. Our recent study further revealed that combined PMP amyloid-venous venular tortuosity index may predict verbal memory loss in subjects with cognitive decline. With these revolutionary findings, we aim to uniquely advance the field of Neuro-Ophthalmology by affording earlier and more accessible visualization of Alzheimer’s disease-associated Aβ via the retina and by using a multimodal detection approach that incorporates vasculature and Aβ measures, allowing for prompter and more sensitive therapeutic intervention as well as pragmatic utility of RFI in clinical settings.
What promising research is poised to change the standard of treatment for Alzheimer's disease?
Our research findings illustrate the intimate interaction between the immune system and CNS, as well as the neuroprotective benefits of boosting the innate immune response to upregulate the body’s inherent ability to self-repair. In the past, Neuro-Immunology was vastly understudied as a field due to the misconception that the blood-brain-barrier blocks communication between the brain and immune system. As you can see, our comprehension of the body’s interconnectivity is growing and changing with such innovative research findings. Accordingly, research examining various treatment modalities such as immunomodulation are shifting toward alleviating disease pathology rather than solely providing symptom relief.
What is it like to be a Student member for the ANA? How has the ANA helped your education and career steps?
As a student member of the ANA, I presented a virtual poster discussing our project titled “Retinal Amyloid Count as a Predictor of Hippocampal Volume and Cognitive Score: A Cohort Study” at the ANA2020 Virtual Annual Meeting.
With many pandemic-related closures and conference cancellations, ANA’s virtual conference platform allowed me to share our research findings, to expand my knowledge about neuro-specific research advancements, and to network with multiple neuro-enthusiasts. I believe that the beauty of education is growth, and as a student I have always aspired to transform unfamiliarity into strength and skill. Doing so is highly dependent on exposure and innovative drive, which are tremendously heightened by supportive mentorship from intellectual and accomplished scientific leaders like Professor Maya Koronyo-Hamaoui and Dr. Oana Dumitrascu as well as by resourceful associations like the ANA.
Want to learn about more of the groundbreaking research being conducted by ANA members? Read past editions of The ANA Q&A.