Distinctive roles of different {beta}-amyloid 42 aggregates in modulation of synaptic functions

Chiang, H-C., Iijima, K., Hakker, I., Zhong, Y. (June 2009) Distinctive roles of different {beta}-amyloid 42 aggregates in modulation of synaptic functions. FASEB J., 23 (6). pp. 1969-1977.

URL: https://www.ncbi.nlm.nih.gov/pubmed/19255256
DOI: 10.1096/fj.08-121152


To determine how endogenously secreted {beta}-amyloid 42 (A{beta}42) aggregates regulate synaptic functions, we examined effects of A{beta}42 at the neuromuscular junction of Drosophila larvae. Voltage-clamp recordings of synaptic transmission and optical analysis of vesicle recycling at presynaptic terminals show that expression of A{beta}42 in neurons leads to a reduction of neurotransmitter release. However, expression of A{beta}42 in postsynaptic muscle cells enhanced neurotransmitter release. Both effects are neutralized by A{beta} antibody, suggesting a role for secreted A{beta}42 peptides. Application of exogenously prepared A{beta}42 oligomers leads to a reduction in synaptic responses, whereas mixed A{beta}42 aggregates with mainly fibrils elicit an opposite effect by increasing synaptic transmission. Further analysis of long-term depression (LTD) confirms differential effects of different A{beta}42 aggregates. Taken together, our data suggest that A{beta}42 is secreted from neurons primarily as oligomers that inhibit neurotransmitter release and exert no effect on LTD. Whereas larger-sized aggregates, possibly fibrils, are major components secreted from muscle cells, which enhance synaptic transmission and LTD. Thus, different types of cells may secrete distinct forms of A{beta}42 aggregates, leading to different modulation of synaptic functions.--Chiang, H.-C., Iijima, K., Hakker, I., Zhong, Y. Distinctive roles of different {beta}-amyloid 42 aggregates in modulation of synaptic functions.

Item Type: Paper
Uncontrolled Keywords: Alzheimer's disease Drosophila neuromuscular junction endogenous
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
CSHL Authors:
Communities: CSHL labs > Zhong lab
Depositing User: CSHL Librarian
Date: 1 June 2009
Date Deposited: 29 Mar 2012 19:19
Last Modified: 13 Mar 2018 16:58
PMCID: PMC2698658
Related URLs:
URI: https://repository.cshl.edu/id/eprint/25593

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