title: Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer's disease.
abstract: The accumulation of beta amyloid (Aβ) can cause synaptic impairments, but the characteristics and mechanisms of the synaptic impairment induced by the accumulation of Aβ in Alzheimer's disease (AD) remain unclear. In identified single neurons in a newly developed Drosophila AD model, in which Aβ accumulates intraneuronally, we found an age-dependent reduction in the synaptic vesicle release probability that was associated with a decrease in the density of presynaptic calcium channel clusters and an increase in the presynaptic and postsynaptic contact length. Moreover, these alterations occurred in the absence of presynaptic bouton loss. In addition, we found that Aβ expression also produced an age-dependent decrease in the amount of Bruchpilot (Brp), which plays an important role in controlling Ca(2+) channel clustering and synaptic vesicle release in the presynaptic active zone. Our study indicates that the chronic accumulation of intraneuronal Aβ can induce functional and structural changes in the presynaptic active zone prior to a loss of presynaptic buttons in the same neuron.
authors.affiliation: Department of Neurology, The Sixth People's Hospital affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Huang
authors.forename: Ping-Li
authors.initials: PL
authors.lastname: Ma
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Ji
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Zhao
authors.forename: Jiang-Xiu
authors.initials: JX
authors.lastname: Tan
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Sun
authors.forename: Fu-De
authors.initials: FD
authors.lastname: Huang
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides