Reduced O-glycosylated clathrin assembly protein AP180: implication for synaptic vesicle recycling dysfunction in Alzheimer's disease.
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.
Department of Neurobiology and Anatomy, University of Rochester Medical Center, NY 14642, USA. pamela_yao@urmc.rochester.edu
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Coleman
D000117:Acetylglucosamine / Q000032:analysis / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002966:Clathrin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005690:Galactose / Q000493:pharmacokinetics; D006031:Glycosylation; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism; D016900:Neurofilament Proteins / Q000032:analysis; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D011233:Precipitin Tests; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*; D016708:Synaptophysin / Q000032:analysis; D014316:Tritium
D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D004791:Enzyme Inhibitors; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D010750:Phosphoproteins; D016708:Synaptophysin; C439023:clathrin assembly protein AP180; D014316:Tritium; C061195:neurofilament protein M; D000117:Acetylglucosamine; D005690:Galactose