Accelerated Aging in the Down Syndrome Brain Indicated by Plasma Biomarkers Showing Greatly Increased Rates of Age‐ and Sex‐Associated Neurodegeneration (UCH‐L1 and NfL) and Astrogliosis (GFAP) and by Heightened Neuronal Apoptosis in a Mouse Model of

Age-associated increases in plasma measures of the rate of neuronal death/damage and astrogliosis/inflammation in people with DS compared to normosomic individuals and of neuronal apoptosis in a mouse model of DS indicate an accelerated rate of brain aging, likely caused by increased APP expression and consequent production of neurotoxic Ab and exacerbated by astrogliosis/inflammation. Clinical trials are indicated for testing whether GM-CSF (sargramostim) treatment may reduce neuronal death/damage and gliosis and improve cognition in young adults with DS and in typical normosomic aging individuals.