Research and Mentoring Meet In Natural Sciences (RAMMINS) Seminar Talk

Dr. Vaishnavi Nagarajan, an assistant professor of biology in the School of Natural Sciences, will present "Novel C. elegans model of Familial Alzheimer’s Disease: Neurodegeneration Markers."

All are welcome to this biology talk. Refreshments will be provided. 

Abstract: Alzheimer’s Disease (AD) is a neurodegenerative disease that causes memory loss, cognitive decline and language problems. AD is the most common cause of dementia. Familial AD is associated with mutations in APP, PSEN1 or PSEN2 (Hatami et al., 2017). PSEN1 or PSEN2 protein form the catalytic unit of ɣ-secretase enzyme (Ferrari & Sorbi, 2021). Although pathological hallmarks and clinical manifestation of FAD and sporadic AD are similar, the important difference is the early age of onset in FAD.  The earliest age at which onset of FAD is seen lies between 35 to 55 years of age (Ryan & Rossor, 2010). In addition, investigating the genetic and pathophysiological mechanisms of genetic AD will have wide-ranging implications in the treatment of AD. It has been reported that the stalled enzyme-substrate (ɣ-secretase – APP) complex, independent of Aβ42 is implicated in disease pathology. In this study, transgenic Caenorhabditis elegans expressing FAD mutant proteins display synaptic degeneration. Based on this observation, I propose to study physiological and behavioral changes occurring in this in vivo FAD model. In humans, AD manifests as impairment in learning and memory, cognitive and behavior leading to loss of verbal and motor control in the end stages (Kent et al., 2020; Long & Holtzman, 2019). C. elegans is a nematode (worm model) that has been used extensively as a model for neurodegenerative studies due to several advantages. C. elegans has a small nervous system with only 302 neurons. Neural connectivity has been established making it an excellent model for learning and memory experiments. Conserved genes and biochemical pathways, short lifespan, along with the ability to express fluorescent proteins in specific cells and tissues using specific promoters are features that collectively make this a suitable model to study disease pathogenesis (Alexander et al., 2014; Alvarez et al., 2022). Therefore, the new C. elegans system provides a powerful platform to gain insights into the functional effects of FAD mutations and consequently to establish future mechanistic studies and therapeutic screening in Alzheimer’s disease.