Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2

Pei Wang, Guang Yang, Dennis R. Mosier, Paul Chang, Tahire Zaidi, Yan Dao Gong, Nan Ming Zhao, Bertha Dominguez, Kuo Fen Lee, Wen Biao Gan, Hui Zheng

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1219-1225
Number of pages7
JournalJournal of Neuroscience
Volume25
Issue number5
DOIs
StatePublished - Feb 2 2005

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Knock-out mice
  • Neuromuscular junction
  • Synaptic transmission
  • Synaptic vesicles

ASJC Scopus subject areas

  • Neuroscience(all)

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