PMID:16541076

Citation	Lesné, S, Koh, MT, Kotilinek, L, Kayed, R, Glabe, CG, Yang, A, Gallagher, M and Ashe, KH (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440:352-7
Abstract	Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-beta precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-beta protein amyloidosis. Young Tg2576 mice (< 6 months old) have normal memory and lack neuropathology, middle-aged mice (6-14 months old) develop memory deficits without neuronal loss, and old mice (> 14 months old) form abundant neuritic plaques containing amyloid-beta (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56). Abeta*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.
Links	PubMed Online version:10.1038/nature04533
Keywords	Alzheimer Disease/genetics; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Amyloid beta-Peptides/chemistry; Amyloid beta-Peptides/genetics; Amyloid beta-Peptides/metabolism; Amyloid beta-Peptides/pharmacology; Animals; Brain/metabolism; Brain/pathology; Brain/physiopathology; Humans; Maze Learning/drug effects; Maze Learning/physiology; Memory/drug effects; Memory/physiology; Mice; Molecular Weight; Plaque, Amyloid/chemistry; Plaque, Amyloid/genetics; Plaque, Amyloid/metabolism; Plaque, Amyloid/pathology; Protein Structure, Quaternary; Rats; Solubility; Time Factors
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:A4	involved_in	GO:0007613: memory	ECO:0000316: genetic interaction evidence used in manual assertion	ComplexPortal:CPX-1134	P		Seeded From UniProt	complete
HUMAN:A4	part_of	GO:0005615: extracellular space	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:A4	part_of	GO:0005623: cell	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:A4	part_of	GO:0016020: membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:A4	involved_in	GO:0090647: modulation of age-related behavioral decline	ECO:0000304: author statement supported by traceable reference used in manual assertion		P	causally_upstream_of:(GO:0007611)	Seeded From UniProt	complete

References

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