Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau.
Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and tau pathology. We extracted pure populations of tau oligomers directly from the cerebral cortex of Alzheimer disease (AD) brain. These oligomers are potent inhibitors of long term potentiation (LTP) in hippocampal brain slices and disrupt memory in wild type mice. We observed for the first time that these authentic brain-derived tau oligomers propagate abnormal tau conformation of endogenous murine tau after prolonged incubation. The conformation and hydrophobicity of tau oligomers play a critical role in the initiation and spread of tau pathology in the naïve host in a manner reminiscent of sporadic AD.
George P. and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555-1045, USA.
Cristian A
CA
Lasagna-Reeves
Diana L
DL
Castillo-Carranza
Urmi
U
Sengupta
Marcos J
MJ
Guerrero-Munoz
Takaki
T
Kiritoshi
Volker
V
Neugebauer
George R
GR
Jackson
Rakez
R
Kayed
D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry* / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011487:Protein Conformation; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012996:Solutions; D016875:tau Proteins / Q000302:isolation & purification / Q000494:pharmacology*
D011994:Recombinant Proteins; D012996:Solutions; D016875:tau Proteins