PMID:26704708

Citation	Kim, Y, Choi, H, Lee, W, Park, H, Kam, TI, Hong, SH, Nah, J, Jung, S, Shin, B, Lee, H, Choi, TY, Choo, H, Kim, KK, Choi, SY, Kayed, R and Jung, YK (2016) Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model. Neurobiol. Dis. 87:19-28
Abstract	In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in transgenic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates.
Links	PubMed Online version:10.1016/j.nbd.2015.12.006
Keywords	Animals; Avoidance Learning/drug effects; Avoidance Learning/physiology; Brain/drug effects; Brain/metabolism; Brain/pathology; Caspases/metabolism; Cell Line, Tumor; Dendritic Spines/drug effects; Dendritic Spines/metabolism; Dendritic Spines/pathology; Disease Models, Animal; Female; Humans; Male; Maze Learning/drug effects; Maze Learning/physiology; Memory Disorders/drug therapy; Memory Disorders/metabolism; Memory Disorders/pathology; Mice, Transgenic; Neurons/drug effects; Neurons/metabolism; Nootropic Agents/pharmacology; Protein Multimerization/drug effects; Protein Multimerization/physiology; Recognition (Psychology)/drug effects; Recognition (Psychology)/physiology; Sirolimus/pharmacology; Spatial Memory/drug effects; Spatial Memory/physiology; tau Proteins/genetics; tau Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TAU	involved_in	GO:0007611: learning or memory	ECO:0000315: mutant phenotype evidence used in manual assertion		P	happens_during:(UBERON:0000112)|happens_during:(UBERON:0018241)	Seeded From UniProt	complete
HUMAN:TAU	involved_in	GO:0051260: protein homooligomerization	ECO:0000315: mutant phenotype evidence used in manual assertion		P	happens_during:(UBERON:0000112) happens_during:(GO:0018105) occurs_in:(UBERON:0002421) regulates:(GO:0007611)|happens_during(UBERON:0018241) happens_during:(GO:0018105) occurs_in:(UBERON:0002421) regulates:(GO:0007611)	Seeded From UniProt	complete
HUMAN:TAU	involved_in	GO:0007416: synapse assembly	ECO:0000315: mutant phenotype evidence used in manual assertion		P	happens_during:(UBERON:0000112) occurs_in:(UBERON:0003883) regulates:(GO:0007611)|happens_during(UBERON:0018241) occurs_in:(UBERON:0003883) regulates:(GO:0007611)	Seeded From UniProt	complete

References

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