Tau suppression in a neurodegenerative mouse model improves memory function.
Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.
Santacruz
K
K
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Lewis
J
J
Spires
T
T
Paulson
J
J
Kotilinek
L
L
Ingelsson
M
M
Guimaraes
A
A
DeTure
M
M
Ramsden
M
M
McGowan
E
E
Forster
C
C
Yue
M
M
Orne
J
J
Janus
C
C
Mariash
A
A
Kuskowski
M
M
Hyman
B
B
Hutton
M
M
Ashe
K H
KH
D000375:Aging; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003071:Cognition; D018450:Disease Progression; D004318:Doxycycline / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016875:tau Proteins; D004318:Doxycycline