Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 5, Pages 1219-1225Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4660-04.2005
Keywords
Alzheimer's disease; amyloid precursor protein; neuromuscular junction; synaptic vesicles; synaptic transmission; knock-out mice
Categories
Funding
- NIA NIH HHS [R01 AG020670, AG21141, R01 AG021141, AG20670] Funding Source: Medline
- NINDS NIH HHS [NS40039, R01 NS040039, R01 NS041846, NS041846] Funding Source: Medline
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Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease ( AD) pathogenesis. Although mutations in the APP gene lead to dominant inheritance of familial AD, the normal function of APP remains elusive. Here, we report that the APP family of proteins plays an essential role in the development of neuromuscular synapses. Mice deficient in APP and its homolog APP-like protein 2 (APLP2) exhibit aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals is dramatically reduced. These structural abnormalities are accompanied by defective neurotransmitter release and a high incidence of synaptic failure. Our results identify APP/APLP2 as key regulators of structure and function of developing neuromuscular synapses.
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