Reduced O-glycosylated clathrin assembly protein AP180: implication for synaptic vesicle recycling dysfunction in Alzheimer's disease

Neurosci Lett. 1998 Aug 7;252(1):33-6. doi: 10.1016/s0304-3940(98)00547-3.

Abstract

Synapse loss is one of the neuropathologies in Alzheimer's disease (AD) that may play a crucial role in the mechanism of its distinct cognitive impairment and dementia. In a previous study [18], a significant reduction of O-glycosylated clathrin assembly protein AP180 was observed in neocortex of AD. The reduction correlated with the density of neurofibrillary tangles. In this study we further determine that the O-GlcNAc/AP180 ratio is not changed, but the level of AP180 protein decreases in AD. Furthermore, whereas the level of neurofilament (NF-M) remains relatively unchanged, another clathrin assembly protein, AP-2, is also reduced in AD along with a small loss of synaptophysin. Our findings suggest that synaptic vesicle recycling dysfunction may be involved in the pathology of synapse loss in AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosamine / analysis
  • Acetylglucosamine / metabolism
  • Adaptor Proteins, Vesicular Transport
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Clathrin / metabolism*
  • Enzyme Inhibitors / metabolism*
  • Galactose / pharmacokinetics
  • Glycosylation
  • Humans
  • Monomeric Clathrin Assembly Proteins*
  • Nerve Tissue Proteins / isolation & purification
  • Nerve Tissue Proteins / metabolism*
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / metabolism
  • Neurofilament Proteins / analysis
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Precipitin Tests
  • Synapses / chemistry
  • Synapses / metabolism
  • Synaptic Vesicles / chemistry
  • Synaptic Vesicles / metabolism*
  • Synaptophysin / analysis
  • Tritium

Substances

  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • Enzyme Inhibitors
  • Monomeric Clathrin Assembly Proteins
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • Phosphoproteins
  • Synaptophysin
  • clathrin assembly protein AP180
  • Tritium
  • neurofilament protein M
  • Acetylglucosamine
  • Galactose