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.
Yao
P J
PJ
Department of Neurobiology and Anatomy, University of Rochester Medical Center, NY 14642, USA. pamela_yao@urmc.rochester.edu
Coleman
P D
PD
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