title: Tau reduction prevents Abeta-induced defects in axonal transport.
abstract: Amyloid-β (Aβ) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of Aβ and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. Aβ oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects.
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA. kvossel@gladstone.ucsf.edu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Jens
authors.initials: J
authors.lastname: Brodbeck
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Daub
authors.forename: Punita
authors.initials: P
authors.lastname: Sharma
authors.forename: Steven
authors.initials: S
authors.lastname: Finkbeiner
authors.forename: Bianxiao
authors.initials: B
authors.lastname: Cui
authors.forename: Lennart
authors.initials: L
authors.lastname: Mucke
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001370:Axonal Transport; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D020917:Receptor, trkA / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D020917:Receptor, trkA