Overexpression of amyloid precursor protein in adipose tissue from patients with Trisomy 21
Study ID: STU-2020-0502
This single site prospective cohort study will assess the impact of triplicate aPP expression on adipose tissue function in youth with Trisomy 21 compared to age-, gender-, and weight-matched youth without Trisomy 21. The primary endpoint is the between group (Down syndrome vs. controls) difference in mitochondrial respiration in adipocytes. The proposed[?]sample size[?]is appropriate for the[?]exploratory[?]nature of the[?]study. in addition, gene expression analysis will be performed to establish overexpression of aPP.
To assess the impact of amyloid precursor protein on adipose tissue function in patients with Trisomy 21 and compare to age and weight matched patients without Trisomy 21. amyloid precursor protein has been shown to compromise the mitochondrial function of white adipose tissue in the setting of a high fat diet (HFD) in mice1. Rodent studies reveal that a high fat diet induces an unconventional mislocalization of aPP to mitochondria which blocks the protein import machinery and ultimately results in obesity. Mice overexpressing adipocyte-specific and mitochondria-targeted aPP display increased body mass and reduced insulin sensitivity, along with dysfunctional adipose tissue, demonstrated by adipose hypertrophy. elimination of adipocyte aPP rescues HFD-impaired mitochondrial function with considerable protection from weight gain and systemic metabolic deficiency. The impact of aPP overexpression in human adipose tissue has not been studied. We hypothesize that aPP over expression will negatively impact the adipose tissue mitochondrial function in humans, similar to the phenomenon observed in mice.