Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila

Zhao, Wang, Tan, Huang, Zhang, Zhang, Wang, YangCheng, Zhu, Sun, Huang (2010) Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila J Neurosci (IF: 5.3) 30(4) 1512-22

Abstract

Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of beta amyloid(1-42) (Abeta) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Abeta accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Abeta. The depletion of presynaptic mitochondria was the earliest detected phenotype and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Abeta-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Abeta accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6633795
http://www.ncbi.nlm.nih.gov/pubmed/20107079
http://dx.doi.org/10.1523/JNEUROSCI.3699-09.2010

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