Cellular Phenotyping of Hippocampal Progenitors Exposed to Patient Serum Predicts Progression to Alzheimer's Disease
73 Pages Posted: 30 Sep 2019 Sneak Peek Status: Review CompleteMore...
The generation of neurons persists into adulthood in the human hippocampus and is modulated by the circulatory systemic environment. Hippocampal neurogenesis is important for learning and memory and altered early in Alzheimer’s Disease (AD). Evaluating hippocampal neurogenic processes during AD progression could therefore be a biomarker for early disease detection. Here, we used a human hippocampal progenitor cell line to evaluate in vitro over time the neurogenic impact of the systemic milieu (i.e. serum) of individuals with mild cognitive impairment (MCI) as they either progressed to AD or remained stable. Cellular phenotyping and linear mixed effects models for repeated measures revealed that decreased proliferation, increased cell death and neurogenesis characterized progression from MCI to AD. Using stepwise logistic regression and machine learning we show that these baseline cellular readouts are significant predictors of progression from MCI to AD.
Keywords: Hippocampal neurogenesis, human hippocampal progenitor cells, Stem cells, serum, Alzheimer's Disease, Mild Cognitive Impairment, biomarker
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