Impact of Wild-Type Hematopoietic Stem and Progenitor Cell Transplantation on Alzheimer’s Disease Mouse Model after Disease Onset

Committee Members

• Dr. Ralph Feuer, Chair (Biology)
• Dr. Stephanie Cherqui (UCSD) 
• Dr. Cristal Zuniga (Biology)
• Dr. John Love (Biochemistry)

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder and is the most common cause of dementia. Despite AD being a common disease, there are still no effective therapies. Recent studies reveal the important role of microglia and neuroinflammation in AD pathology in increasing Aβ production, degradation of the blood-brain barrier, and dysfunction of endothelial cells. Our lab has previously shown that a single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation of mice at 2 months of age rescued the AD phenotype in 5xFAD mice and that the transplantation fully rescued the disease phenotype leading to the preservation of memory and neurocognitive performance, reduction of the Aβ plaque burden in hippocampus and cortex, and preventing microgliosis and neuroinflammation at 4-month post-transplantation (6 months of age).

This study aims to investigate that single systemic WT HSPC transplantation into adult 5xFAD mice either halts or improves neurocognitive function after AD onset by transplanting older 5xFAD mice at 6 months of age. That is, this work aims to show that the transplantation of WT HSPCs could result in healthy microglia as a long-term treatment that might lighten the impact of AD after onset. We have transplanted WT HSPC into adult 5xFAD mice to analyze AD pathobiology, neurocognitive function, and microglia in rescuing AD-associated complications to further reveal the potential of HSPC transplantation to treat AD after disease onset. Since the fields of HSPC transplantation and microglia continue to advance, our potential contributions could increase understanding of AD-associated complications leading to more accurate targeted therapies for AD including long-term treatments after disease onset.