@entity4943 ( @entity4943 ) is caused by mutations in MAPT, the gene encoding tau. @entity4943 begins with executive function deficits and other @entity146 , which progress to @entity303 . Neurodegenerative changes include accumulation of aggregated tau as neuronal and glial fibrillary tangles. Aggregated tau is seen in numerous other @entity179 , including @entity195 ( @entity195 ). We expressed normal and @entity4943 mutant @entity1 tau (mutations @entity18824 and @entity69188 ) in @entity2199 to model @entity74 . Tau pan-neuronal expression caused progressive uncoordinated locomotion (Unc), characteristic of nervous @entity3002 in worms. Subsequently, insoluble tau accumulates and both soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in @entity4943 , @entity195 , and other @entity13859 . @entity179 , seen as bulges and gaps in nerve cords followed by @entity528 , occurs after insoluble tau begins to accumulate. Axons show vacuoles, membranous infoldings, and whorls with associated amorphous tau accumulations and @entity1423 . @entity4943 mutation lines had a more severe Unc phenotype, accumulated more insoluble tau at a younger age, were more resistant to cholinergic inhibitors, and had more severe @entity528 when compared with lines expressing normal tau. The Unc phenotype is caused by a presynaptic defect. Postsynaptic transmission is intact. This transgenic model will enable mechanistic dissection of tau-induced @entity179 and identification of genes and compounds that inhibit pathological tau formation.

@entity179 and defective neurotransmission in a XXXX model of @entity13859 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity2199 :: ('6239', 'Species') :: ['Caenorhabditis elegans'] @entity146 :: ('MESH:D001523', 'Disease') :: ['abnormal behaviors'] @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia'] @entity13859 :: ('MESH:D024801', 'Disease') :: ['tauopathies'] @entity1423 :: ('MESH:D001791', 'Disease') :: ['abnormal tau-positive aggregates'] @entity3002 :: ('MESH:D009421', 'Disease') :: ['system defects'] @entity18824 :: ('p|SUB|P|301|L', 'ProteinMutation') :: ['P301L'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegeneration', 'neurodegenerative diseases', 'Substantial neurodegeneration'] @entity74 :: ('MESH:D030342', 'Disease') :: ['tauopathy disorders'] @entity69188 :: ('p|SUB|V|337|M', 'ProteinMutation') :: ['V337M'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity4943 :: ('MESH:D057180', 'Disease') :: ['FTDP-17', 'Frontotemporal dementia with parkinsonism chromosome 17 type'] @entity528 :: ('MESH:D009410', 'Disease') :: ['loss of neurons', 'axonal degeneration']
@entity2199 :: (6239,Species) :: ['Caenorhabditis elegans']
