Differentiated Alzheimer's Disease Transmitochondrial Cybrid Cell Lines Exhibit Reduced Organelle Movement

Abstract

The axonal transport and function of organelles like mitochondria and lysosomes may be impaired and play an important role in the pathogenesis of Alzheimer's disease (AD). Unique cybrid cell lines that model AD pathology were created by fusing platelets containing mitochondria from age-matched AD and control volunteers with mitochondrial DNA-free SH-SY5Y human neuroblastoma cells. These cybrid lines were differentiated to form process-bearing neuronal cells. Mitochondria and lysosomes in the neurites of each cybrid line were fluorescently labeled to determine the kinetics of organelle movement. The mitochondria in AD cybrid neurites were elongate, whereas the mitochondria in control cybrid neurites were short and more punctate. The mean velocity of mitochondrial movement, as well as the percentage of moving mitochondria, was significantly reduced in AD cybrids. The velocity of lysosomal movement was also reduced in the processes of AD cybrid cells, suggesting that the axonal transport machinery may be compromised in cybrid cell lines that contain mitochondrial DNA derived from AD patients. Reduced mitochondrial and lysosomal movement in susceptible neurons may compromise function in metabolically demanding structures like synaptic terminals and participate in the terminal degeneration that is characteristic of AD.