Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model.
Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Abeta-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Abeta levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.
Roberson
Erik D
ED
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA. eroberson@gladstone.ucsf.edu
Scearce-Levie
Kimberly
K
Palop
Jorge J
JJ
Yan
Fengrong
F
Cheng
Irene H
IH
Wu
Tiffany
T
Gerstein
Hilary
H
Yu
Gui-Qiu
GQ
Mucke
Lennart
L
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005106:Exploratory Behavior; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D010433:Pentylenetetrazole / Q000494:pharmacology; D010766:Phosphorylation; D012640:Seizures / Q000517:prevention & control; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D016875:tau Proteins; D007608:Kainic Acid; D010433:Pentylenetetrazole