Maina's Group

Ancestry plays a crucial role in the risk of developing human diseases, including Alzheimer’s Disease and Related Dementias (AD/ADRD). Despite this, most AD/ADRD research predominantly relies on models drawn from European ancestry populations, even though over 60% of current dementia cases occur in low- and middle-income countries. This is confounded by the lack of access to human samples from most parts of Africa due to cultural and religious views that hinder organ donations, including the donation of post-mortem human brains, a resource of critical value in dementia research. To address this, we leverage the power of human induced pluripotent stem cells (hiPSCs) due to their ability to capture the genetic diversity of the donor population. Our work focuses on generating and using hiPSCs from indigenous Africans to study the mechanisms of ADRD. Our approach incorporates genetics, cell biology, imaging, and biochemistry, enabling us to compare our results with data from other populations.

Pertinent to this, our past research has identified a deleterious role for amyloid beta on the nucleolus and discovered a nucleolar role for the microtubule associate protein tau, a key player involved in various forms of dementia known as tauopathies. Our studies reveal that tau regulates rDNA transcription and the nucleolar stress response. Given that ancestry also influences rDNA variation, our work further delves into understanding how genetic background impacts nucleolar function and the role of tau in the nucleolus in both health and disease.