Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome

Abstract In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer-type. Upregulation of p53 and APO-1/Fas (CD95) precedes apoptosis in many cell types, and a potential role for these molecules has already been demonstrated in Alzheimer's disease (AD) and several other neurodegenerative diseases. We measured p53 and APO-1/Fas (CD95) protein in four different regions of cerebral cortex and cerebellum in nine adult DS patients with Alzheimer-like neuropathologic lesions compared to nine controls. Quantitative ELISA demonstrated higher frontal lobe (mean±SD: 0.10±0.035 vs. 0.041±0.016 ng/mg protein), temporal lobe (0.062±0.021 vs. 0.032±0.019 ng/mg protein) and cerebellar levels (0.078±0.030 vs. 0.039±0.032 ng/mg protein) of p53 protein, and higher temporal lobe (mean±SD: 12.3±4.3 vs. 5.3±2.0 U/mg protein) and cerebellar levels (5.9±1.4 vs. 2.9±1.1 U/mg protein) of APO-1/Fas (CD95) protein. The results suggest that p53- or APO-1/Fas (CD95)-associated apoptosis may be an important feature of neurodegeneration in DS.