Alzheimer’s disease (AD), the most common form of dementia is one of the leading causes of death worldwide. To date, no cure has been found. The world is in desperate need of a solution. Down syndrome (DS) individuals suffer from an early onset of Alzheimer’s disease (AD) and share the neuropathology. There is a lack of understanding in the fundamental biology of how gene interactions lead to defects in higher functions of the brain such as memory, learning and social behaviour. My research has focussed on the two genes- the regulator of calcineurin-1 (RCAN1) and apolipoprotein E (ApoE). RCAN1 is overexpressed in AD brains, it has a role in mitochondrial structure and function, and endosomal trafficking. ApoE 4 is the risk factor for AD.  In this study, I used human differentiated neuronal cells and a brain organoid model derived from commercially available human induced pluripotent cells (iPSC). A brain organoid is the closest model to an in vivo system, as studying events in a living brain is impossible. I used CRISPR/Cas9 and transfection to generate ApoE and over-expressed RCAN1 cohorts. The Lattice Light-sheet microscopy capable of imaging deeper and the spinning disc confocal microscopy was used to identify structural and functional differences between the groups. This study promises a detailed map of how RCAN1 and ApoE interactions affect cognition in the brain. 

Nakisa Malakooti is an emerging leader and scientist in the field of cognitive decline. She has expertise in stem cell biology, Down syndrome and Alzheimer’s disease. Her dedication to solving the mystery of AD and finding a cure led her to look closer into the connection between DS and AD. She has years of experience in research and teaching. She is passionate about her research and finding a cure for Alzheimer’s disease in both DS and non-DS individuals. Since November 2021, she is a Jerome LeJune research flow at the Monash BDI, focusing on gene interactions in the cognitive decline in Down syndrome. She aims to understand how structural changes lead to functional changes resulting in cognitive decline. One of the challenges in the field of neuroscience is that the events in the brain cannot be monitored. She employs stem cell biology and brain organoid for her research which is the closest model to the actual human brain to study these events.