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

Authors:
Xiao-Liang Zhao
Xiao-Liang Zhao
Shandong University
China
Wen-An Wang
Wen-An Wang
University of Alberta
Canada
Xiao Zhang
Xiao Zhang
Peking University School and Hospital of Stomatology
China
Bao-Zhu Zhang
Bao-Zhu Zhang
Nankai University
China
Yu-Hang Wang
Yu-Hang Wang
Shandong University
China
Han-Yu YangCheng
Han-Yu YangCheng
Shanghai Institutes for Biological Sciences
China

J Neurosci 2010 Jan;30(4):1512-22

Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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.

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http://dx.doi.org/10.1523/JNEUROSCI.3699-09.2010DOI Listing
January 2010
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